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

    Summary
    EudraCT number
    		 2017-001762-13
    Trial protocol
    		 ES   DE   BE   HU   EE   LT   IT  
    Global end of trial date
    09 Jul 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Jul 2022
    First version publication date
    24 Jul 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    747-401
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03633227
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Intercept Pharmaceuticals, Inc.
    Sponsor organisation address
    305 Madison Avenue, Morristown, NJ, United States, 07960
    Public contact
    Medical Information, Intercept Pharmaceuticals, Inc., +1 844-782-4278, medinfo@interceptpharma.com
    Scientific contact
    Medical Information, Intercept Pharmaceuticals, Inc., +1 844-782-4278, medinfo@interceptpharma.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 Jun 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Jul 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the pharmacokinetics (PK) of Obeticholic acid (OCA) and its conjugates, glycine 6α-ethyl chenodeoxycholic acid (glyco-OCA) and taurine 6α-ethyl chenodeoxycholic acid (tauro-OCA), and OCA metabolite glucuronide (OCA-glucuronide) compared with placebo. To evaluate the safety and tolerability of OCA treatment compared with placebo.
    Protection of trial subjects
    The study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Council for Harmonisation (ICH)/Good Clinical Practice (GCP), applicable regulatory requirements and the Sponsor’s policies.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Estonia: 1
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Lithuania: 2
    Country: Number of subjects enrolled
    United States: 8
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Brazil: 2
    Country: Number of subjects enrolled
    Argentina: 4
    Worldwide total number of subjects
    22
    EEA total number of subjects
    7
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    12
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at study sites in the United States, Argentina, Belgium, Spain, Lithuania, Brazil, Australia, Germany, Estonia, Italy, Canada, and Hungary.

    Pre-assignment
    Screening details
    		 A total of 31 participants were screened and 22 participants were randomized.

    Period 1
    Period 1 title
    Double Blind (DB), up to Week 48
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    OCA matching placebo was administered per schedule specified in the arm description.

    Arm title
    		 Obeticholic Acid (OCA)
    Arm description
    		 Participants initiated treatment with OCA 5 milligrams (mg) tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Obeticholic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    OCA was administered per dose and schedule specified in the arm description.

    Number of subjects in period 1
    		Placebo Obeticholic Acid (OCA)
    Started
    12
    10
    Completed
    4
    6
    Not completed
    8
    4
         Physician decision
    1
    -
         Consent withdrawn by subject
    1
    1
         Adverse event, non-fatal
    -
    1
         Death
    2
    1
         Multiple Serious AE and Drug Interruptions
    1
    -
         Study Terminated by Sponsor
    2
    1
         Liver Transplant During the Course of the Study
    1
    -
    Period 2
    Period 2 title
    DB Extension, Week 48 up to 3 Years
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants, who had completed their 48-week treatment, could continue the treatment until all randomized participants had completed their 48-week treatment period and the database for that period was locked (total duration: approximately up to 3 years).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    OCA matching placebo was administered per the schedule specified in the arm description.

    Arm title
    		 Obeticholic Acid (OCA)
    Arm description
    		 Participants, who had completed their 48-week treatment, could continue the treatment until all randomized participants had completed their 48-week treatment period and the database for that period was locked (total duration: approximately up to 3 years).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Obeticholic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    OCA was administered per dose and schedule specified in the arm description.

    Number of subjects in period 2
    		Placebo Obeticholic Acid (OCA)
    Started
    4
    6
    Completed
    0
    0
    Not completed
    4
    6
         Consent withdrawn by subject
    -
    2
         Physician decision
    -
    1
         Death
    -
    1
         Study Terminated by Sponsor
    3
    2
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks.

    Reporting group title
    Obeticholic Acid (OCA)
    Reporting group description
    		 Participants initiated treatment with OCA 5 milligrams (mg) tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks.

    Reporting group values
    		 Placebo Obeticholic Acid (OCA) Total
    Number of subjects
    		 12 10 22
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.5 ( 9.10 ) 60.5 ( 10.19 ) -
    Gender categorical
    Units: Subjects
        Female
    		 10 6 16
        Male
    		 2 4 6
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 6 4 10
        Not Hispanic or Latino
    		 6 6 12
        Unknown or Not Reported
    		 0 0 0
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 1
        Asian
    		 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 0 0 0
        White
    		 11 10 21
    Child-Pugh Score Component Category (Ascites Categories)
    Number of participants with Child-Pugh component - ascites categories of none, mild, and moderate-severe has been reported. The assessment of ascites was based on the investigator’s discretion.
    Units: Subjects
        None
    		 6 5 11
        Mild
    		 5 3 8
        Moderate to Severe
    		 1 2 3
    Child-Pugh Score Component Category (Prothrombin Time Categories)
    Number of participants with Child-Pugh component - prothrombin time (measured as INR) in categories of <1.7, 1.7 - 2.3, and >2.3 has been reported.
    Units: Subjects
        <1.7
    		 12 10 22
        1.7-2.3
    		 0 0 0
        >2.3
    		 0 0 0
    Child-Pugh Score Component Category (Serum Albumin Categories)
    Number of participants with Child-Pugh component - serum albumin levels in categories of >35 gram per liter (g/L), 28-35 g/L, or <28 g/L has been reported.
    Units: Subjects
        >35 gram per liter (g/L)
    		 3 4 7
        28 - 35 g/L
    		 8 5 13
        <28 g/L
    		 1 1 2
    Child-Pugh Score Component Category (Total Bilirubin Categories)
    Number of participants with Child-Pugh component - total bilirubin levels in categories of <34 micromole per liter (µmol/L), 34-50 µmol/L, and >50 µmol/L has been reported.
    Units: Subjects
        <34 micromole per liter (µmol/L)
    		 3 5 8
        34-50 µmol/L
    		 5 0 5
        >50 µmol/L
    		 4 5 9
    Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
    Grade 0: normal consciousness, normal personality, normal neurological examination, normal electroencephalogram. Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles, per second (cps) waves. Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves. Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves. Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cps delta activity.
    Units: Subjects
        Grade 0
    		 7 7 14
        Grade 1 or 2
    		 5 3 8
        Grade 3 or 4
    		 0 0 0
    Model of End-stage Liver Disease (MELD) Score
    The MELD scoring system is used to assess the severity of chronic liver disease. The MELD score is derived from the participant’s serum total bilirubin, serum creatinine, and prothrombin international normalized ratio (INR): 3.78×log normal (ln) [total bilirubin (mg/deciliter [dL])] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
    Units: Score on a scale
        median (inter-quartile range (Q1-Q3))
    		 11.75 (10.60 to 13.50) 12.75 (9.50 to 16.00) -
    MELD-Sodium (Na) Score
    The MELD-Na scoring system is used to assess the severity of chronic liver disease in the participants with an initial MELD(i) score greater than 11. MELD-Na score is derived from the participant’s serum total bilirubin, serum creatinine, INR, and sodium. The MELD-Na score is re-calculated as follows: MELD-Na = MELD(i) + 1.32*(137-Na) – [0.033*MELD(i)*(137-Na)]. MELD score ranges from 6-40 with higher scores indicating more severe liver disease and a worse outcome.
    Units: score on a scale
        median (inter-quartile range (Q1-Q3))
    		 11.75 (10.60 to 14.25) 13.25 (9.50 to 16.00) -
    Child-Pugh Score
    The Child-Pugh classification was a scoring system used for the classification of the severity of cirrhosis. It included three continuous variables (bilirubin, albumin, and INR) and two discrete variables (ascites and encephalopathy). Each variable was scored 1-3 with 3 indicating most severe derangement. The determination of Child-Pugh score ranged from 5 to 15. The higher the score, the sicker the participant.
    Units: score on a scale
        median (inter-quartile range (Q1-Q3))
    		 8.0 (7.0 to 8.0) 8.0 (7.0 to 8.0) -
    Total Bilirubin
    Units: μmol/L
        median (inter-quartile range (Q1-Q3))
    		 45.38 (34.57 to 55.79) 41.50 (19.00 to 106.88) -
    Direct Bilirubin
    Units: μmol/L
        median (inter-quartile range (Q1-Q3))
    		 21.58 (15.37 to 37.18) 25.50 (8.00 to 76.00) -
    Alkaline Phosphatase
    Units: unit per liter (U/L)
        median (inter-quartile range (Q1-Q3))
    		 216.0 (144.5 to 290.0) 267.5 (151.0 to 381.0) -
    Alanine Aminotransferase
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 47.5 (31.0 to 60.5) 38.0 (27.0 to 56.0) -
    Aspartate Aminotransferase
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 60.0 (45.5 to 95.5) 65.5 (46.0 to 104.0) -
    Gamma Glutamyl Transferase
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 98.0 (36.0 to 152.0) 103.0 (53.0 to 191.0) -
    Prothrombin INR
    Units: INR
        median (inter-quartile range (Q1-Q3))
    		 1.15 (1.10 to 1.20) 1.23 (1.10 to 1.30) -
    Creatinine
    Units: µmol/L
        median (inter-quartile range (Q1-Q3))
    		 60.000 (51.000 to 96.732) 60.172 (55.000 to 95.472) -
    Albumin
    Units: gram per liter (g/L)
        median (inter-quartile range (Q1-Q3))
    		 34.50 (33.00 to 36.75) 33.00 (30.00 to 36.50) -
    Platelets
    Number analyzed (n) for Placebo arm = 11 Number analyzed (n) for OCA arm = 9
    Units: 10^9/L
        median (inter-quartile range (Q1-Q3))
    		 141.5 (80.0 to 160.5) 132.5 (84.5 to 158.5) -
    Total Bile Acids Concentration
    Total bile acids (micromole [μM]) = total ursodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total cholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM. Number analyzed (n) for Placebo arm = 11
    Units: μM
        median (inter-quartile range (Q1-Q3))
    		 149 (90.3 to 307) 127 (65.3 to 176) -
    Total Endogenous Bile Acids Concentration
    Number analyzed (n) for Placebo arm = 11
    Units: μM
        median (inter-quartile range (Q1-Q3))
    		 64.7 (29.4 to 75.2) 42.1 (18.6 to 69.6) -
    7α-hydroxy-4-cholesten-3-one (C4)
    Number analyzed (n) for Placebo arm = 11
    Units: ng/mL
        median (inter-quartile range (Q1-Q3))
    		 0.708 (0.372 to 5.16) 0.814 (0.472 to 2.09) -
    Fibroblast Growth Factor-19 (FGF-19)
    Number analyzed (n) for Placebo arm = 11
    Units: picograms per milliliter (pg/mL)
        median (inter-quartile range (Q1-Q3))
    		 278 (105 to 618) 163 (139 to 359) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks.

    Reporting group title
    Obeticholic Acid (OCA)
    Reporting group description
    		 Participants initiated treatment with OCA 5 milligrams (mg) tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks.
    Reporting group title
    Placebo
    Reporting group description
    		 Participants, who had completed their 48-week treatment, could continue the treatment until all randomized participants had completed their 48-week treatment period and the database for that period was locked (total duration: approximately up to 3 years).

    Reporting group title
    Obeticholic Acid (OCA)
    Reporting group description
    		 Participants, who had completed their 48-week treatment, could continue the treatment until all randomized participants had completed their 48-week treatment period and the database for that period was locked (total duration: approximately up to 3 years).

    Subject analysis set title
    OCA 5 mg Once Weekly
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received OCA 5 mg tablets orally once weekly.

    Subject analysis set title
    OCA 5 mg Twice Weekly
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received OCA 5 mg tablets orally twice weekly.

    Subject analysis set title
    OCA 10 mg Twice Weekly
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received OCA 10 mg tablets orally twice weekly.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks. Participants, who had completed their 48-Week treatment, could continue the treatment until all randomized participants had completed their 48-Week treatment period and the database for that period was locked (total duration: approximately up to 3 years).

    Subject analysis set title
    Obeticholic Acid (OCA)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants initiated treatment with OCA 5 mg tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks. Participants, who had completed their 48-Week treatment, could continue the treatment until all randomized participants had completed their 48-Week treatment period and the database for that period was locked (total duration: approximately up to 3 years).

    Primary: Maximum Observed Concentration (Cmax) of Total OCA at Week 12

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    End point title
    		 Maximum Observed Concentration (Cmax) of Total OCA at Week 12 [1]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. Analysis population description (APD): PK Population: participants who received OCA and had adequate concentration-time profile to characterize OCA and its conjugates and must not have had any major protocol deviations that potentially affect exposure level. Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [2]
    0 [3]
    Units: Nanogram per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    293 ( 189 )
    ( )
    ( )
    Notes
    [2] - No participant started OCA 5 mg twice weekly at Week 12.
    [3] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Time to Maximum Concentration (Tmax) of Total OCA at Week 12

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    End point title
    		 Time to Maximum Concentration (Tmax) of Total OCA at Week 12 [4]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [5]
    0 [6]
    Units: hours
        median (full range (min-max))
    2.02 (2.00 to 3.00)
    ( to )
    ( to )
    Notes
    [5] - No participant started OCA 5 mg twice weekly at Week 12.
    [6] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Trough Concentration (Ctrough) of Total OCA at Week 12

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    End point title
    		 Trough Concentration (Ctrough) of Total OCA at Week 12 [7]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 12. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 12
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [8]
    0 [9]
    Units: nanogram per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    77.6 ( 49.7 )
    ( )
    ( )
    Notes
    [8] - No participant started OCA 5 mg twice weekly at week 12.
    [9] - No participant started OCA 10 mg twice weekly at week 12.
    No statistical analyses for this end point

    Primary: Area Under the Concentration Versus Time Curve From Zero Time to 24 Hours (AUC0-24h) of Total OCA at Week 12

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    End point title
    		 Area Under the Concentration Versus Time Curve From Zero Time to 24 Hours (AUC0-24h) of Total OCA at Week 12 [10]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [11]
    0 [12]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    2970 ( 1650 )
    ( )
    ( )
    Notes
    [11] - No participant started OCA 5 mg twice weekly at Week 12.
    [12] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Cmax of Total OCA at Week 18

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    End point title
    		 Cmax of Total OCA at Week 18 [13]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [14]
    Units: ng/mL
        arithmetic mean (standard deviation)
    136 ( 77.6 )
    406 ( 120 )
    ( )
    Notes
    [14] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Tmax of Total OCA at Week 18

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    End point title
    		 Tmax of Total OCA at Week 18 [15]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [16]
    Units: hours
        median (full range (min-max))
    0.750 (0.500 to 1.00)
    2.52 (2.00 to 3.03)
    ( to )
    Notes
    [16] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Ctrough of Total OCA at Week 18

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    End point title
    		 Ctrough of Total OCA at Week 18 [17]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 18. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 18
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [18]
    Units: ng/mL
        arithmetic mean (standard deviation)
    28.7 ( 13.6 )
    187 ( 147 )
    ( )
    Notes
    [18] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: AUC0-24h of Total OCA at Week 18

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    End point title
    		 AUC0-24h of Total OCA at Week 18 [19]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [20]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    1380 ( 776 )
    5810 ( 3600 )
    ( )
    Notes
    [20] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Cmax of Total OCA at Week 24

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    End point title
    		 Cmax of Total OCA at Week 24 [21]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [22]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    263 ( 261 )
    195 ( 99999 )
    622 ( 117 )
    Notes
    [22] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of Total OCA at Week 24

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    End point title
    		 Tmax of Total OCA at Week 24 [23]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1
    2
    Units: hours
        median (full range (min-max))
    5.04 (4.00 to 6.08)
    0.750 (0.750 to 0.750)
    2.27 (2.00 to 2.53)
    No statistical analyses for this end point

    Primary: Ctrough of Total OCA at Week 24

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    End point title
    		 Ctrough of Total OCA at Week 24 [24]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 24. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 24
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [25]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    132 ( 163 )
    41.4 ( 99999 )
    435 ( 28.6 )
    Notes
    [25] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of Total OCA at Week 24

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    End point title
    		 AUC0-24h of Total OCA at Week 24 [26]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [27]
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    4500 ( 4910 )
    2020 ( 99999 )
    11300 ( 2950 )
    Notes
    [27] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Total OCA at Week 30

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    End point title
    		 Cmax of Total OCA at Week 30 [28]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [29]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    125 ( 99999 )
    277 ( 64.7 )
    674 ( 310 )
    Notes
    [29] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of Total OCA at Week 30

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    End point title
    		 Tmax of Total OCA at Week 30 [30]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1
    2
    2
    Units: hours
        median (full range (min-max))
    1.00 (1.00 to 1.00)
    4.52 (4.03 to 5.00)
    3.77 (2.53 to 5.00)
    No statistical analyses for this end point

    Primary: Ctrough of Total OCA at Week 30

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    End point title
    		 Ctrough of Total OCA at Week 30 [31]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 30. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 30
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [32]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    22.3 ( 99999 )
    217 ( 15.7 )
    317 ( 248 )
    Notes
    [32] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of Total OCA at Week 30

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    End point title
    		 AUC0-24h of Total OCA at Week 30 [33]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [34]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    1260 ( 99999 )
    5040 ( 855 )
    10500 ( 7000 )
    Notes
    [34] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Total OCA at Week 48

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    End point title
    		 Cmax of Total OCA at Week 48 [35]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [36]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    200 ( 15.1 )
    728 ( 27.5 )
    Notes
    [36] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Tmax of Total OCA at Week 48

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    End point title
    		 Tmax of Total OCA at Week 48 [37]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [38]
    2
    2
    Units: hours
        median (full range (min-max))
    ( to )
    1.73 (1.47 to 2.00)
    4.03 (2.00 to 6.05)
    Notes
    [38] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Ctrough of Total OCA at Week 48

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    End point title
    		 Ctrough of Total OCA at Week 48 [39]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 48. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 48
    Notes
    [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [40]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    88.3 ( 29.9 )
    497 ( 135 )
    Notes
    [40] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: AUC0-24h of Total OCA at Week 48

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    End point title
    		 AUC0-24h of Total OCA at Week 48 [41]
    End point description
    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [42]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    ( )
    3210 ( 56.7 )
    13900 ( 452 )
    Notes
    [42] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Cmax of Unconjugated OCA at Week 12

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    End point title
    		 Cmax of Unconjugated OCA at Week 12 [43]
    End point description
    APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [44]
    0 [45]
    Units: ng/mL
        arithmetic mean (standard deviation)
    107 ( 62.0 )
    ( )
    ( )
    Notes
    [44] - No participant started OCA 5 mg twice weekly at Week 12.
    [45] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Tmax of Unconjugated OCA at Week 12

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    End point title
    		 Tmax of Unconjugated OCA at Week 12 [46]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [47]
    0 [48]
    Units: hours
        median (full range (min-max))
    1.43 (1.00 to 1.50)
    ( to )
    ( to )
    Notes
    [47] - No participant started OCA 5 mg twice weekly at Week 12.
    [48] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Ctrough of Unconjugated OCA at Week 12

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    End point title
    		 Ctrough of Unconjugated OCA at Week 12 [49]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 12. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 12
    Notes
    [49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [50]
    0 [51]
    Units: ng/mL
        arithmetic mean (standard deviation)
    2.92 ( 2.51 )
    ( )
    ( )
    Notes
    [50] - No participant started OCA 5 mg twice weekly at Week 12.
    [51] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: AUC0-24h of Unconjugated OCA at Week 12

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    End point title
    		 AUC0-24h of Unconjugated OCA at Week 12 [52]
    End point description
    AUC0-24 was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    3
    0 [53]
    0 [54]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    278 ( 142 )
    ( )
    ( )
    Notes
    [53] - No participant started OCA 5 mg twice weekly at Week 12.
    [54] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Cmax of Unconjugated OCA at Week 18

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    End point title
    		 Cmax of Unconjugated OCA at Week 18 [55]
    End point description
    Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [55] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [56]
    Units: ng/mL
        arithmetic mean (standard deviation)
    107 ( 47.4 )
    109 ( 90.3 )
    ( )
    Notes
    [56] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Tmax of Unconjugated OCA at Week 18

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    End point title
    		 Tmax of Unconjugated OCA at Week 18 [57]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [57] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [58]
    Units: hours
        median (full range (min-max))
    0.750 (0.500 to 1.00)
    1.24 (1.00 to 1.48)
    ( to )
    Notes
    [58] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Ctrough of Unconjugated OCA at Week 18

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    End point title
    		 Ctrough of Unconjugated OCA at Week 18 [59]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 18. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 18
    Notes
    [59] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [60]
    Units: ng/mL
        arithmetic mean (standard deviation)
    3.38 ( 0.262 )
    3.56 ( 4.01 )
    ( )
    Notes
    [60] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: AUC0-24h of Unconjugated OCA at Week 18

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    End point title
    		 AUC0-24h of Unconjugated OCA at Week 18 [61]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [61] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [62]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    191 ( 125 )
    263 ( 247 )
    ( )
    Notes
    [62] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Cmax of Unconjugated OCA at Week 24

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    End point title
    		 Cmax of Unconjugated OCA at Week 24 [63]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [63] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [64]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    115 ( 98.2 )
    157 ( 99999 )
    168 ( 92.6 )
    Notes
    [64] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of Unconjugated OCA at Week 24

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    End point title
    		 Tmax of Unconjugated OCA at Week 24 [65]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [65] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1
    2
    Units: hours
        median (full range (min-max))
    1.13 (0.750 to 1.50)
    0.500 (0.500 to 0.500)
    1.63 (1.58 to 1.67)
    No statistical analyses for this end point

    Primary: Ctrough of Unconjugated OCA at Week 24

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    End point title
    		 Ctrough of Unconjugated OCA at Week 24 [66]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 24. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 24
    Notes
    [66] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [67]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    2.46 ( 2.05 )
    5.18 ( 99999 )
    8.77 ( 11.4 )
    Notes
    [67] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of Unconjugated OCA at Week 24

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    End point title
    		 AUC0-24h of Unconjugated OCA at Week 24 [68]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [68] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [69]
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    235 ( 130 )
    345 ( 99999 )
    480 ( 414 )
    Notes
    [69] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Unconjugated OCA at Week 30

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    End point title
    		 Cmax of Unconjugated OCA at Week 30 [70]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [70] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [71]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    92.6 ( 99999 )
    132 ( 24.0 )
    115 ( 40.9 )
    Notes
    [71] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of Unconjugated OCA at Week 30

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    End point title
    		 Tmax of Unconjugated OCA at Week 30 [72]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [72] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1
    2
    2
    Units: hours
        median (full range (min-max))
    0.750 (0.750 to 0.750)
    1.17 (1.00 to 1.33)
    1.75 (0.500 to 3.00)
    No statistical analyses for this end point

    Primary: Ctrough of Unconjugated OCA at Week 30

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    End point title
    		 Ctrough of Unconjugated OCA at Week 30 [73]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 30. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 30
    Notes
    [73] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [74]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    3.03 ( 99999 )
    4.27 ( 4.85 )
    3.20 ( 3.14 )
    Notes
    [74] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of Unconjugated OCA at Week 30

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    End point title
    		 AUC0-24h of Unconjugated OCA at Week 30 [75]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [75] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [76]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    176 ( 99999 )
    304 ( 82.3 )
    473 ( 397 )
    Notes
    [76] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Unconjugated OCA at Week 48

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    End point title
    		 Cmax of Unconjugated OCA at Week 48 [77]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [77] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [78]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    131 ( 31.8 )
    284 ( 177 )
    Notes
    [78] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Tmax of Unconjugated OCA at Week 48

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    End point title
    		 Tmax of Unconjugated OCA at Week 48 [79]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [79] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [80]
    2
    2
    Units: hours
        median (full range (min-max))
    ( to )
    1.10 (0.700 to 1.50)
    0.500 (0.500 to 0.500)
    Notes
    [80] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Ctrough of Unconjugated OCA at Week 48

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    End point title
    		 Ctrough of Unconjugated OCA at Week 48 [81]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 48. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 48
    Notes
    [81] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [82]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    3.43 ( 3.90 )
    4.72 ( 6.67 )
    Notes
    [82] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: AUC0-24h of Unconjugated OCA at Week 48

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    End point title
    		 AUC0-24h of Unconjugated OCA at Week 48 [83]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [83] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [84]
    2
    1 [85]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    ( )
    376 ( 118 )
    1190 ( 99999 )
    Notes
    [84] - No participant received OCA 5 mg once weekly at Week 48.
    [85] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Glyco-OCA at Week 12

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    End point title
    		 Cmax of Glyco-OCA at Week 12 [86]
    End point description
    APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [86] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [87]
    0 [88]
    Units: ng/mL
        arithmetic mean (standard deviation)
    117 ( 55.0 )
    ( )
    ( )
    Notes
    [87] - No participant started OCA 5 mg twice weekly at Week 12.
    [88] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Tmax of Glyco-OCA at Week 12

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    End point title
    		 Tmax of Glyco-OCA at Week 12 [89]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [89] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [90]
    0 [91]
    Units: hours
        median (full range (min-max))
    5.00 (3.92 to 5.00)
    ( to )
    ( to )
    Notes
    [90] - No participant started OCA 5 mg twice weekly at Week 12.
    [91] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Ctrough of Glyco-OCA at Week 12

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    End point title
    		 Ctrough of Glyco-OCA at Week 12 [92]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 12. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 12
    Notes
    [92] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [93]
    0 [94]
    Units: ng/mL
        arithmetic mean (standard deviation)
    47.1 ( 31.1 )
    ( )
    ( )
    Notes
    [93] - No participant started OCA 5 mg twice weekly at Week 12.
    [94] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: AUC0-24h of Glyco-OCA at Week 12

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    End point title
    		 AUC0-24h of Glyco-OCA at Week 12 [95]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [95] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [96]
    0 [97]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    1690 ( 947 )
    ( )
    ( )
    Notes
    [96] - No participant started OCA 5 mg twice weekly at Week 12.
    [97] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Metabolite to Parent Ratio of AUC-0-24h (MRAUC) of Glyco-OCA at Week 12

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    End point title
    		 Metabolite to Parent Ratio of AUC-0-24h (MRAUC) of Glyco-OCA at Week 12 [98]
    End point description
    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [98] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    3
    0 [99]
    0 [100]
    Units: ratio
        arithmetic mean (standard deviation)
    4.36 ( 1.03 )
    ( )
    ( )
    Notes
    [99] - No participant started OCA 5 mg twice weekly at Week 12.
    [100] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Metabolite to Parent Ratio of Cmax (MRCmax) of Glyco-OCA at Week 12

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    End point title
    		 Metabolite to Parent Ratio of Cmax (MRCmax) of Glyco-OCA at Week 12 [101]
    End point description
    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [101] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [102]
    0 [103]
    Units: ratio
        arithmetic mean (standard deviation)
    1.39 ( 1.38 )
    ( )
    ( )
    Notes
    [102] - No participant started OCA 5 mg twice weekly at Week 12.
    [103] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Cmax of Glyco-OCA at Week 18

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    End point title
    		 Cmax of Glyco-OCA at Week 18 [104]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [104] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [105]
    Units: ng/mL
        arithmetic mean (standard deviation)
    52.7 ( 4.31 )
    213 ( 22.6 )
    ( )
    Notes
    [105] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Tmax of Glyco-OCA at Week 18

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    End point title
    		 Tmax of Glyco-OCA at Week 18 [106]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [106] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [107]
    Units: hours
        median (full range (min-max))
    4.25 (2.50 to 6.00)
    2.52 (2.00 to 3.03)
    ( to )
    Notes
    [107] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Ctrough of Glyco-OCA at Week 18

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    End point title
    		 Ctrough of Glyco-OCA at Week 18 [108]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 18. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 18
    Notes
    [108] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [109]
    Units: ng/mL
        arithmetic mean (standard deviation)
    13.3 ( 5.03 )
    98.1 ( 53.7 )
    ( )
    Notes
    [109] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: AUC0-24h of Glyco-OCA at Week 18

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    End point title
    		 AUC0-24h of Glyco-OCA at Week 18 [110]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [110] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [111]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    625 ( 147 )
    3020 ( 1120 )
    ( )
    Notes
    [111] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: MRAUC of Glyco-OCA at Week 18

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    End point title
    		 MRAUC of Glyco-OCA at Week 18 [112]
    End point description
    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [112] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [113]
    Units: ratio
        arithmetic mean (standard deviation)
    3.39 ( 1.55 )
    21.2 ( 23.6 )
    ( )
    Notes
    [113] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: MRCmax of Glyco-OCA at Week 18

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    End point title
    		 MRCmax of Glyco-OCA at Week 18 [114]
    End point description
    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [114] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [115]
    Units: ratio
        arithmetic mean (standard deviation)
    0.487 ( 0.250 )
    2.73 ( 2.44 )
    ( )
    Notes
    [115] - No participant started OCA 10 mg twice weekly at Week 18.
    No statistical analyses for this end point

    Primary: Cmax of Glyco-OCA at Week 24

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    End point title
    		 Cmax of Glyco-OCA at Week 24 [116]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [116] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [117]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    166 ( 163 )
    56.2 ( 99999 )
    294 ( 70.0 )
    Notes
    [117] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of Glyco-OCA at Week 24

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    End point title
    		 Tmax of Glyco-OCA at Week 24 [118]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [118] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1
    2
    Units: hours
        median (full range (min-max))
    5.04 (4.00 to 6.08)
    5.00 (5.00 to 5.00)
    4.54 (4.08 to 5.00)
    No statistical analyses for this end point

    Primary: Ctrough of Glyco-OCA at Week 24

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    End point title
    		 Ctrough of Glyco-OCA at Week 24 [119]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 24. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 24
    Notes
    [119] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [120]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    83.0 ( 106 )
    22.0 ( 99999 )
    239 ( 7.07 )
    Notes
    [120] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of Glyco-OCA at Week 24

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    End point title
    		 AUC0-24h of Glyco-OCA at Week 24 [121]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [121] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [122]
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    2710 ( 3030 )
    936 ( 99999 )
    5550 ( 878 )
    Notes
    [122] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRAUC of Glyco-OCA at Week 24

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    End point title
    		 MRAUC of Glyco-OCA at Week 24 [123]
    End point description
    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [123] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [124]
    2
    Units: ratio
        arithmetic mean (standard deviation)
    8.26 ( 6.80 )
    2.39 ( 99999 )
    17.3 ( 16.5 )
    Notes
    [124] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of Glyco-OCA at Week 24

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    End point title
    		 MRCmax of Glyco-OCA at Week 24 [125]
    End point description
    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [125] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [126]
    2
    Units: ratio
        arithmetic mean (standard deviation)
    1.17 ( 0.253 )
    0.315 ( 99999 )
    1.94 ( 1.44 )
    Notes
    [126] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Glyco-OCA at Week 30

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    End point title
    		 Cmax of Glyco-OCA at Week 30 [127]
    End point description
    APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [127] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [128]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    83.0 ( 99999 )
    174 ( 75.0 )
    301 ( 86.3 )
    Notes
    [128] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of Glyco-OCA at Week 30

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    End point title
    		 Tmax of Glyco-OCA at Week 30 [129]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [129] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1
    2
    2
    Units: hours
        median (full range (min-max))
    6.00 (6.00 to 6.00)
    14.0 (4.03 to 24.0)
    4.51 (4.02 to 5.00)
    No statistical analyses for this end point

    Primary: Ctrough of Glyco-OCA at Week 30

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    End point title
    		 Ctrough of Glyco-OCA at Week 30 [130]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 30. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 30
    Notes
    [130] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [131]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    14.4 ( 99999 )
    143 ( 30.4 )
    156 ( 79.4 )
    Notes
    [131] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of Glyco-OCA at Week 30

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    End point title
    		 AUC0-24h of Glyco-OCA at Week 30 [132]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [132] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [133]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    863 ( 99999 )
    3180 ( 1080 )
    5050 ( 2260 )
    Notes
    [133] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRAUC of Glyco-OCA at Week 30

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    End point title
    		 MRAUC of Glyco-OCA at Week 30 [134]
    End point description
    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [134] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [135]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    4.31 ( 99999 )
    10.0 ( 5.84 )
    17.2 ( 18.7 )
    Notes
    [135] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of Glyco-OCA at Week 30

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    End point title
    		 MRCmax of Glyco-OCA at Week 30 [136]
    End point description
    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [136] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [137]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    0.789 ( 99999 )
    1.23 ( 0.723 )
    2.58 ( 1.58 )
    Notes
    [137] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Glyco-OCA at Week 48

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    End point title
    		 Cmax of Glyco-OCA at Week 48 [138]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [138] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [139]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    123 ( 34.0 )
    354 ( 37.5 )
    Notes
    [139] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Tmax of Glyco-OCA at Week 48

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    End point title
    		 Tmax of Glyco-OCA at Week 48 [140]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [140] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [141]
    2
    2
    Units: hours
        median (full range (min-max))
    ( to )
    5.00 (5.00 to 5.00)
    4.03 (2.00 to 6.05)
    Notes
    [141] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Ctrough of Glyco-OCA at Week 48

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    End point title
    		 Ctrough of Glyco-OCA at Week 48 [142]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 48. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 48
    Notes
    [142] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [143]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    65.9 ( 10.2 )
    280 ( 62.2 )
    Notes
    [143] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: AUC0-24h of Glyco-OCA at Week 48

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    End point title
    		 AUC0-24h of Glyco-OCA at Week 48 [144]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [144] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [145]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    ( )
    2120 ( 442 )
    6950 ( 648 )
    Notes
    [145] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: MRAUC of Glyco-OCA at Week 48

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    End point title
    		 MRAUC of Glyco-OCA at Week 48 [146]
    End point description
    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [146] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [147]
    2
    1 [148]
    Units: ratio
        arithmetic mean (standard deviation)
    ( )
    5.39 ( 2.69 )
    4.79 ( 99999 )
    Notes
    [147] - No participant received OCA 5 mg once weekly at Week 48.
    [148] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of Glyco-OCA at Week 48

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    End point title
    		 MRCmax of Glyco-OCA at Week 48 [149]
    End point description
    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [149] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [150]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    ( )
    0.826 ( 0.0280 )
    1.41 ( 1.00 )
    Notes
    [150] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Cmax of Tauro-OCA at Week 12

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    End point title
    		 Cmax of Tauro-OCA at Week 12 [151]
    End point description
    APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [151] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [152]
    0 [153]
    Units: ng/mL
        arithmetic mean (standard deviation)
    201 ( 213 )
    ( )
    ( )
    Notes
    [152] - No participant started OCA 5 mg twice weekly at Week 12.
    [153] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Tmax of Tauro-OCA at Week 12

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    End point title
    		 Tmax of Tauro-OCA at Week 12 [154]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [154] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [155]
    0 [156]
    Units: hours
        median (full range (min-max))
    5.00 (3.00 to 5.00)
    ( to )
    ( to )
    Notes
    [155] - No participant started OCA 5 mg twice weekly at Week 12.
    [156] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Ctrough of Tauro-OCA at Week 12

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    End point title
    		 Ctrough of Tauro-OCA at Week 12 [157]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 12. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 12
    Notes
    [157] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [158]
    0 [159]
    Units: ng/mL
        arithmetic mean (standard deviation)
    41.6 ( 33.0 )
    ( )
    ( )
    Notes
    [158] - No participant started OCA 5 mg twice weekly at Week 12.
    [159] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: AUC0-24h of Tauro-OCA at Week 12

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    End point title
    		 AUC0-24h of Tauro-OCA at Week 12 [160]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [160] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [161]
    0 [162]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    1580 ( 1260 )
    ( )
    ( )
    Notes
    [161] - No participant started OCA 5 mg twice weekly at Week 12.
    [162] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: MRAUC of Tauro-OCA at Week 12

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    End point title
    		 MRAUC of Tauro-OCA at Week 12 [163]
    End point description
    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [163] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    3
    0 [164]
    0 [165]
    Units: ratio
        arithmetic mean (standard deviation)
    3.13 ( 1.08 )
    ( )
    ( )
    Notes
    [164] - No participant started OCA 5 mg twice weekly at Week 12.
    [165] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: MRCmax of Tauro-OCA at Week 12

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    End point title
    		 MRCmax of Tauro-OCA at Week 12 [166]
    End point description
    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [166] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [167]
    0 [168]
    Units: ratio
        arithmetic mean (standard deviation)
    2.24 ( 2.46 )
    ( )
    ( )
    Notes
    [167] - No participant started OCA 5 mg twice weekly at Week 12.
    [168] - No participant started OCA 10 mg twice weekly at Week 12.
    No statistical analyses for this end point

    Primary: Cmax of Tauro-OCA at Week 18

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    End point title
    		 Cmax of Tauro-OCA at Week 18 [169]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [169] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [170]
    Units: ng/mL
        arithmetic mean (standard deviation)
    63.2 ( 46.9 )
    221 ( 188 )
    ( )
    Notes
    [170] - No participant started OCA 10 mg twice weekly at Week 18
    No statistical analyses for this end point

    Primary: Tmax of Tauro-OCA at Week 18

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    End point title
    		 Tmax of Tauro-OCA at Week 18 [171]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [171] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [172]
    Units: hours
        median (full range (min-max))
    5.00 (5.00 to 5.00)
    2.52 (2.00 to 3.03)
    ( to )
    Notes
    [172] - No participant started OCA 10 mg twice weekly at Week 18
    No statistical analyses for this end point

    Primary: Ctrough of Tauro-OCA at Week 18

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    End point title
    		 Ctrough of Tauro-OCA at Week 18 [173]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 18. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 18
    Notes
    [173] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [174]
    Units: ng/mL
        arithmetic mean (standard deviation)
    17.0 ( 11.2 )
    122 ( 130 )
    ( )
    Notes
    [174] - No participant started OCA 10 mg twice weekly at Week 18
    No statistical analyses for this end point

    Primary: AUC0-24h of Tauro-OCA at Week 18

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    End point title
    		 AUC0-24h of Tauro-OCA at Week 18 [175]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [175] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [176]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    799 ( 654 )
    3630 ( 3600 )
    ( )
    Notes
    [176] - No participant started OCA 10 mg twice weekly at Week 18
    No statistical analyses for this end point

    Primary: MRAUC of Tauro-OCA at Week 18

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    End point title
    		 MRAUC of Tauro-OCA at Week 18 [177]
    End point description
    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [177] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [178]
    Units: ratio
        arithmetic mean (standard deviation)
    3.11 ( 0.685 )
    28.8 ( 37.9 )
    ( )
    Notes
    [178] - No participant started OCA 10 mg twice weekly at Week 18
    No statistical analyses for this end point

    Primary: MRCmax of Tauro-OCA at Week 18

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    End point title
    		 MRCmax of Tauro-OCA at Week 18 [179]
    End point description
    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration. Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [179] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [180]
    Units: ratio
        arithmetic mean (standard deviation)
    0.434 ( 0.156 )
    3.32 ( 4.12 )
    ( )
    Notes
    [180] - No participant started OCA 10 mg twice weekly at Week 18
    No statistical analyses for this end point

    Primary: Cmax of Tauro-OCA at Week 24

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    End point title
    		 Cmax of Tauro-OCA at Week 24 [181]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [181] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [182]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    142 ( 144 )
    65.5 ( 99999 )
    430 ( 142 )
    Notes
    [182] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of Tauro-OCA at Week 24

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    End point title
    		 Tmax of Tauro-OCA at Week 24 [183]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [183] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1
    2
    Units: hours
        median (full range (min-max))
    5.54 (5.00 to 6.08)
    9.00 (9.00 to 9.00)
    4.05 (3.10 to 5.00)
    No statistical analyses for this end point

    Primary: Ctrough of Tauro-OCA at Week 24

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    End point title
    		 Ctrough of Tauro-OCA at Week 24 [184]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 24. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 24
    Notes
    [184] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [185]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    71.0 ( 90.5 )
    21.2 ( 99999 )
    271 ( 58.0 )
    Notes
    [185] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of Tauro-OCA at Week 24

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    End point title
    		 AUC0-24h of Tauro-OCA at Week 24 [186]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [186] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [187]
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    2360 ( 2650 )
    1060 ( 99999 )
    7470 ( 3260 )
    Notes
    [187] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRAUC of Tauro-OCA at Week 24

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    End point title
    		 MRAUC of Tauro-OCA at Week 24 [188]
    End point description
    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [188] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [189]
    2
    Units: ratio
        arithmetic mean (standard deviation)
    6.51 ( 5.40 )
    2.46 ( 99999 )
    23.4 ( 25.6 )
    Notes
    [189] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of Tauro-OCA at Week 24

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    End point title
    		 MRCmax of Tauro-OCA at Week 24 [190]
    End point description
    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [190] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [191]
    2
    Units: ratio
        arithmetic mean (standard deviation)
    0.881 ( 0.249 )
    0.332 ( 99999 )
    2.63 ( 2.13 )
    Notes
    [191] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Tauro-OCA at Week 30

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    End point title
    		 Cmax of Tauro-OCA at Week 30 [192]
    End point description
    APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [192] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [193]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    38.6 ( 99999 )
    141 ( 13.4 )
    460 ( 342 )
    Notes
    [193] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of Tauro-OCA at Week 30

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    End point title
    		 Tmax of Tauro-OCA at Week 30 [194]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [194] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1
    2
    2
    Units: hours
        median (full range (min-max))
    6.00 (6.00 to 6.00)
    4.52 (4.03 to 5.00)
    4.03 (3.05 to 5.00)
    No statistical analyses for this end point

    Primary: Ctrough of Tauro-OCA at Week 30

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    End point title
    		 Ctrough of Tauro-OCA at Week 30 [195]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 30. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 30
    Notes
    [195] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [196]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    8.21 ( 99999 )
    110 ( 7.78 )
    222 ( 228 )
    Notes
    [196] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of Tauro-OCA at Week 30

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    End point title
    		 AUC0-24h of Tauro-OCA at Week 30 [197]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [197] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [198]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    408 ( 99999 )
    2430 ( 18.1 )
    7020 ( 6780 )
    Notes
    [198] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRAUC of Tauro-OCA at Week 30

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    End point title
    		 MRAUC of Tauro-OCA at Week 30 [199]
    End point description
    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [199] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [200]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    1.84 ( 99999 )
    6.61 ( 1.74 )
    25.7 ( 33.0 )
    Notes
    [200] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of Tauro-OCA at Week 30

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    End point title
    		 MRCmax of Tauro-OCA at Week 30 [201]
    End point description
    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [201] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [202]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    0.332 ( 99999 )
    0.855 ( 0.0746 )
    3.85 ( 3.73 )
    Notes
    [202] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of Tauro-OCA at Week 48

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    End point title
    		 Cmax of Tauro-OCA at Week 48 [203]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [203] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [204]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    72.5 ( 15.1 )
    485 ( 20.5 )
    Notes
    [204] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Tmax of Tauro-OCA at Week 48

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    End point title
    		 Tmax of Tauro-OCA at Week 48 [205]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [205] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [206]
    2
    2
    Units: hours
        median (full range (min-max))
    ( to )
    6.50 (6.00 to 7.00)
    2.57 (2.00 to 3.13)
    Notes
    [206] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Ctrough of Tauro-OCA at Week 48

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    End point title
    		 Ctrough of Tauro-OCA at Week 48 [207]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 48. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 48
    Notes
    [207] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [208]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    33.7 ( 21.4 )
    309 ( 109 )
    Notes
    [208] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: AUC0-24h of Tauro-OCA at Week 48

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    End point title
    		 AUC0-24h of Tauro-OCA at Week 48 [209]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [209] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [210]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    ( )
    1220 ( 389 )
    8890 ( 696 )
    Notes
    [210] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: MRAUC of Tauro-OCA at Week 48

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    End point title
    		 MRAUC of Tauro-OCA at Week 48 [211]
    End point description
    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [211] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [212]
    2
    1 [213]
    Units: ratio
        arithmetic mean (standard deviation)
    ( )
    2.59 ( 0.00903 )
    5.60 ( 99999 )
    Notes
    [212] - No participant received OCA 5 mg once weekly at Week 48.
    [213] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of Tauro-OCA at Week 48

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    End point title
    		 MRCmax of Tauro-OCA at Week 48 [214]
    End point description
    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [214] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [215]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    ( )
    0.468 ( 0.206 )
    1.67 ( 0.989 )
    Notes
    [215] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Cmax of OCA-glucuronide at Week 12

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    End point title
    		 Cmax of OCA-glucuronide at Week 12 [216]
    End point description
    APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [216] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [217]
    0 [218]
    Units: ng/mL
        arithmetic mean (standard deviation)
    47.0 ( 24.7 )
    ( )
    ( )
    Notes
    [217] - No participant started OCA 5 mg Twice Weekly at Week 12
    [218] - No participant started OCA 10 mg Twice Weekly at Week 12
    No statistical analyses for this end point

    Primary: Tmax of OCA-glucuronide at Week 12

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    End point title
    		 Tmax of OCA-glucuronide at Week 12 [219]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. Pharmacokinetic of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [219] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [220]
    0 [221]
    Units: hours
        median (full range (min-max))
    2.50 (1.50 to 3.00)
    ( to )
    ( to )
    Notes
    [220] - No participant started OCA 5 mg Twice Weekly at Week 12
    [221] - No participant started OCA 10 mg Twice Weekly at Week 12
    No statistical analyses for this end point

    Primary: Ctrough of OCA-glucuronide at Week 12

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    End point title
    		 Ctrough of OCA-glucuronide at Week 12 [222]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 12. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 12
    Notes
    [222] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [223]
    0 [224]
    Units: ng/mL
        arithmetic mean (standard deviation)
    20.7 ( 15.4 )
    ( )
    ( )
    Notes
    [223] - No participant started OCA 5 mg Twice Weekly at Week 12
    [224] - No participant started OCA 10 mg Twice Weekly at Week 12
    No statistical analyses for this end point

    Primary: AUC0-24h of OCA-glucuronide at Week 12

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    End point title
    		 AUC0-24h of OCA-glucuronide at Week 12 [225]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. Pharmacokinetic of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [225] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    4
    0 [226]
    0 [227]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    593 ( 388 )
    ( )
    ( )
    Notes
    [226] - No participant started OCA 5 mg Twice Weekly at Week 12
    [227] - No participant started OCA 10 mg Twice Weekly at Week 12
    No statistical analyses for this end point

    Primary: MRAUC of OCA-glucuronide at Week 12

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    End point title
    		 MRAUC of OCA-glucuronide at Week 12 [228]
    End point description
    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [228] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    3
    0 [229]
    0 [230]
    Units: ratio
        arithmetic mean (standard deviation)
    1.17 ( 0.638 )
    ( )
    ( )
    Notes
    [229] - No participant started OCA 5 mg Twice Weekly at Week 12
    [230] - No participant started OCA 10 mg Twice Weekly at Week 12
    No statistical analyses for this end point

    Primary: MRCmax of OCA-glucuronide at Week 12

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    End point title
    		 MRCmax of OCA-glucuronide at Week 12 [231]
    End point description
    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
    Notes
    [231] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    5
    0 [232]
    0 [233]
    Units: ratio
        arithmetic mean (standard deviation)
    0.384 ( 0.275 )
    ( )
    ( )
    Notes
    [232] - No participant started OCA 5 mg Twice Weekly at Week 12
    [233] - No participant started OCA 10 mg Twice Weekly at Week 12
    No statistical analyses for this end point

    Primary: Cmax of OCA-glucuronide at Week 18

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    End point title
    		 Cmax of OCA-glucuronide at Week 18 [234]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [234] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [235]
    Units: ng/mL
        arithmetic mean (standard deviation)
    39.2 ( 30.3 )
    74.9 ( 38.4 )
    ( )
    Notes
    [235] - No participant started OCA 10 mg Twice Weekly at Week 18
    No statistical analyses for this end point

    Primary: Tmax of OCA-glucuronide at Week 18

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    End point title
    		 Tmax of OCA-glucuronide at Week 18 [236]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [236] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [237]
    Units: hours
        median (full range (min-max))
    1.25 (1.00 to 1.50)
    2.73 (1.50 to 3.97)
    ( to )
    Notes
    [237] - No participant started OCA 10 mg Twice Weekly at Week 18
    No statistical analyses for this end point

    Primary: Ctrough of OCA-glucuronide at Week 18

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    End point title
    		 Ctrough of OCA-glucuronide at Week 18 [238]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 18. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 18
    Notes
    [238] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [239]
    Units: ng/mL
        arithmetic mean (standard deviation)
    11.7 ( 7.55 )
    40.9 ( 43.9 )
    ( )
    Notes
    [239] - No participant started OCA 10 mg Twice Weekly at Week 18
    No statistical analyses for this end point

    Primary: AUC0-24h of OCA-glucuronide at Week 18

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    End point title
    		 AUC0-24h of OCA-glucuronide at Week 18 [240]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [240] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [241]
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    390 ( 278 )
    1120 ( 989 )
    ( )
    Notes
    [241] - No participant started OCA 10 mg Twice Weekly at Week 18
    No statistical analyses for this end point

    Primary: MRAUC of OCA-glucuronide at Week 18

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    End point title
    		 MRAUC of OCA-glucuronide at Week 18 [242]
    End point description
    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [242] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [243]
    Units: ratio
        arithmetic mean (standard deviation)
    1.41 ( 0.101 )
    7.58 ( 9.76 )
    ( )
    Notes
    [243] - No participant started OCA 10 mg Twice Weekly at Week 18
    No statistical analyses for this end point

    Primary: MRCmax of OCA-glucuronide at Week 18

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    End point title
    		 MRCmax of OCA-glucuronide at Week 18 [244]
    End point description
    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration. Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
    Notes
    [244] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    2
    0 [245]
    Units: ratio
        arithmetic mean (standard deviation)
    0.236 ( 0.0942 )
    0.891 ( 0.985 )
    ( )
    Notes
    [245] - No participant started OCA 10 mg Twice Weekly at Week 18
    No statistical analyses for this end point

    Primary: Cmax of OCA-glucuronide at Week 24

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    End point title
    		 Cmax of OCA-glucuronide at Week 24 [246]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [246] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [247]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    20.2 ( 7.42 )
    58.1 ( 99999 )
    127 ( 71.0 )
    Notes
    [247] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of OCA-glucuronide at Week 24

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    End point title
    		 Tmax of OCA-glucuronide at Week 24 [248]
    End point description
    Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [248] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1
    2
    Units: hours
        median (full range (min-max))
    2.54 (2.08 to 3.00)
    1.00 (1.00 to 1.00)
    2.27 (2.00 to 2.53)
    No statistical analyses for this end point

    Primary: Ctrough of OCA-glucuronide at Week 24

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    End point title
    		 Ctrough of OCA-glucuronide at Week 24 [249]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 24. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 24
    Notes
    [249] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [250]
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    11.6 ( 6.43 )
    14.5 ( 99999 )
    84.2 ( 81.7 )
    Notes
    [250] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of OCA-glucuronide at Week 24

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    End point title
    		 AUC0-24h of OCA-glucuronide at Week 24 [251]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [251] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [252]
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    330 ( 191 )
    602 ( 99999 )
    2120 ( 1920 )
    Notes
    [252] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRAUC of OCA-glucuronide at Week 24

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    End point title
    		 MRAUC of OCA-glucuronide at Week 24 [253]
    End point description
    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [253] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [254]
    2
    Units: ratio
        arithmetic mean (standard deviation)
    0.983 ( 0.0286 )
    1.23 ( 99999 )
    6.87 ( 8.74 )
    Notes
    [254] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of OCA-glucuronide at Week 24

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    End point title
    		 MRCmax of OCA-glucuronide at Week 24 [255]
    End point description
    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
    Notes
    [255] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    2
    1 [256]
    2
    Units: ratio
        arithmetic mean (standard deviation)
    0.165 ( 0.0959 )
    0.261 ( 99999 )
    0.727 ( 0.701 )
    Notes
    [256] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of OCA-glucuronide at Week 30

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    End point title
    		 Cmax of OCA-glucuronide at Week 30 [257]
    End point description
    APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [257] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [258]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    13.7 ( 99999 )
    51.9 ( 49.4 )
    148 ( 117 )
    Notes
    [258] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Tmax of OCA-glucuronide at Week 30

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    End point title
    		 Tmax of OCA-glucuronide at Week 30 [259]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [259] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1
    2
    2
    Units: hours
        median (full range (min-max))
    1.50 (1.50 to 1.50)
    2.26 (1.50 to 3.02)
    4.51 (4.02 to 5.00)
    No statistical analyses for this end point

    Primary: Ctrough of OCA-glucuronide at Week 30

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    End point title
    		 Ctrough of OCA-glucuronide at Week 30 [260]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 30. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 30
    Notes
    [260] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [261]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    5.57 ( 99999 )
    19.7 ( 13.8 )
    89.0 ( 107 )
    Notes
    [261] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: AUC0-24h of OCA-glucuronide at Week 30

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    End point title
    		 AUC0-24h of OCA-glucuronide at Week 30 [262]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [262] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [263]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    170 ( 99999 )
    641 ( 482 )
    2200 ( 2100 )
    Notes
    [263] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRAUC of OCA-glucuronide at Week 30

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    End point title
    		 MRAUC of OCA-glucuronide at Week 30 [264]
    End point description
    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [264] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [265]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    0.680 ( 99999 )
    1.39 ( 0.742 )
    7.10 ( 9.09 )
    Notes
    [265] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of OCA-glucuronide at Week 30

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    End point title
    		 MRCmax of OCA-glucuronide at Week 30 [266]
    End point description
    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
    Notes
    [266] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    1 [267]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    0.104 ( 99999 )
    0.257 ( 0.217 )
    1.11 ( 1.11 )
    Notes
    [267] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: Cmax of OCA-glucuronide at Week 48

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    End point title
    		 Cmax of OCA-glucuronide at Week 48 [268]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [268] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [269]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    66.0 ( 63.6 )
    134 ( 71.3 )
    Notes
    [269] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Tmax of OCA-glucuronide at Week 48

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    End point title
    		 Tmax of OCA-glucuronide at Week 48 [270]
    End point description
    APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [270] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [271]
    2
    2
    Units: hours
        median (full range (min-max))
    ( to )
    1.73 (1.47 to 2.00)
    1.54 (1.50 to 1.58)
    Notes
    [271] - No participant OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Ctrough of OCA-glucuronide at Week 48

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    End point title
    		 Ctrough of OCA-glucuronide at Week 48 [272]
    End point description
    Ctrough was considered as the concentration at 24-hours post-dose at Week 48. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    24 hours post-dose at Week 48
    Notes
    [272] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [273]
    2
    2
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    39.2 ( 35.7 )
    89.2 ( 73.3 )
    Notes
    [273] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: AUC0-24h of OCA-glucuronide at Week 48

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    End point title
    		 AUC0-24h of OCA-glucuronide at Week 48 [274]
    End point description
    AUC0-24h was calculated using the linear/linear trapezoidal rule. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [274] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [275]
    2
    2
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    ( )
    952 ( 833 )
    2490 ( 1520 )
    Notes
    [275] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: MRAUC of OCA-glucuronide at Week 48

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    End point title
    		 MRAUC of OCA-glucuronide at Week 48 [276]
    End point description
    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [276] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [277]
    2
    1 [278]
    Units: ratio
        arithmetic mean (standard deviation)
    ( )
    1.62 ( 1.05 )
    0.833 ( 99999 )
    Notes
    [277] - No participant received OCA 5 mg once weekly at Week 48.
    [278] - 99999: Standard deviation is not estimable as there is only one participant.
    No statistical analyses for this end point

    Primary: MRCmax of OCA-glucuronide at Week 48

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    End point title
    		 MRCmax of OCA-glucuronide at Week 48 [279]
    End point description
    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration. APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
    End point type
    Primary
    End point timeframe
    Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
    Notes
    [279] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 OCA 5 mg Once Weekly OCA 5 mg Twice Weekly OCA 10 mg Twice Weekly
    Number of subjects analysed
    0 [280]
    2
    2
    Units: ratio
        arithmetic mean (standard deviation)
    ( )
    0.411 ( 0.444 )
    0.482 ( 0.479 )
    Notes
    [280] - No participant received OCA 5 mg once weekly at Week 48.
    No statistical analyses for this end point

    Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [281]
    End point description
    An adverse event (AE) was any unfavorable & unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study drug, whether or not related to study drug. An SAE was any AE that resulted in death, was life-threatening, resulted in a persistent or significant disability/incapacity, resulted in in-patient hospitalization or prolonged an existing hospitalization, was a congenital anomaly/birth defect, or was an important medical event that could jeopardize participant or could have required medical intervention to prevent one of the outcomes listed above. TEAE was defined as any AE if it met one or more of the following criteria: 1)An AE started on or after first study drug dose & within 30 days after last dose of study drug, 2)An AE occurred prior to first study drug dose that worsens after the first study drug dose. APD: Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo)
    End point type
    Primary
    End point timeframe
    Baseline up to approximately 3 years
    Notes
    [281] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    12
    10
    Units: Participants
        Any TEAE
    12
    10
        SAE
    9
    7
    No statistical analyses for this end point

    Secondary: Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    The MELD scoring system is used to assess the severity of chronic liver disease. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and prothrombin international normalized ratio (INR): 3.78× log normal (ln) [total bilirubin (mg/deciliter [dL])] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome. APD: Intent-to-treat (ITT) population included all randomized participants who received any amount of investigational product (OCA or placebo). Participants with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11 [282]
    10 [283]
    Units: Score on a scale
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    0.50 (-0.50 to 1.00)
    0.00 (-1.50 to 2.00)
        Change at Week 6 (n = 9, 8)
    0.50 (0.00 to 2.50)
    0.00 (-0.75 to 1.25)
        Change at Week 12 (n = 6, 7)
    0.75 (0.00 to 2.50)
    0.00 (-1.00 to 1.00)
        Change at Week 18 (n = 8, 8)
    0.65 (-0.25 to 3.00)
    -0.75 (-2.00 to 1.00)
        Change at Week 24 (n = 4, 5)
    0.15 (0.00 to 0.40)
    -1.50 (-2.00 to 0.00)
        Change at Week 30 (n = 6, 6)
    0.15 (-0.50 to 0.50)
    -1.25 (-2.00 to 0.00)
        Change at Week 36 (n = 6, 6)
    0.15 (-1.00 to 1.50)
    0.25 (-1.50 to 1.00)
        Change at Week 42 (n = 6, 6)
    0.65 (-0.50 to 1.50)
    0.50 (0.00 to 1.50)
        Change at Week 48 (n = 6, 4)
    0.65 (0.00 to 1.50)
    -1.75 (-2.50 to -0.50)
        Change at Extension Month 3 (n = 5, 5)
    0.50 (0.50 to 4.30)
    -1.00 (-1.50 to -0.50)
        Change at Extension Month 6 (n = 3, 2)
    0.00 (-1.00 to 3.50)
    0.25 (0.00 to 0.50)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    0.75 (-1.00 to 2.50)
        Change at Extension Month 12 (n = 1, 1)
    -1.00 (-1.00 to -1.00)
    4.50 (4.50 to 4.50)
        Change at Extension Month 15 (n = 1, 0)
    -1.00 (-1.00 to -1.00)
    99999 (99999 to 99999)
    Notes
    [282] - 99999 denotes data not available as there were no participants at specified timepoint.
    [283] - 99999 denotes data not available as there were no participants at specified timepoint.
    No statistical analyses for this end point

    Secondary: Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    The MELD-Na scoring system is used to assess the severity of chronic liver disease in the participants with an initial MELD(i) score greater than 11. MELD-Na score is derived from the participant's serum total bilirubin, serum creatinine, INR, and sodium. The MELD-Na score is re-calculated as follows: MELD-Na = MELD(i) + 1.32*(137-Na) – [0.033*MELD(i)*(137-Na)]. MELD score ranges from 6-40 with higher scores indicating more severe liver disease and a worse outcome. APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11 [284]
    10 [285]
    Units: Score on a Scale
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    0.00 (-0.50 to 1.00)
    0.50 (-1.50 to 2.00)
        Change at Week 6 (n = 9, 8)
    0.50 (0.00 to 2.00)
    -0.25 (-0.75 to 1.50)
        Change at Week 12 (n = 6, 7)
    0.50 (0.00 to 3.50)
    0.50 (-1.50 to 2.00)
        Change at Week 18 (n = 8, 8)
    0.65 (-0.25 to 2.75)
    -0.75 (-2.50 to 0.50)
        Change at Week 24 (n = 4, 5)
    0.15 (0.00 to 0.40)
    -2.00 (-2.50 to 1.00)
        Change at Week 30 (n = 6, 6)
    0.15 (-0.50 to 0.50)
    -0.75 (-2.00 to 0.50)
        Change at Week 36 (n = 6, 6)
    0.15 (-1.00 to 1.50)
    -0.25 (-1.50 to 1.00)
        Change at Week 42 (n = 5, 6)
    0.00 (-0.50 to 1.30)
    0.50 (0.00 to 0.50)
        Change at Week 48 (n = 6, 4)
    0.65 (0.00 to 2.50)
    -1.75 (-3.00 to 0.00)
        Change at Extension Month 3 (n = 5, 5)
    2.50 (0.50 to 4.30)
    -1.00 (-2.50 to -0.50)
        Change at Extension Month 6 (n = 3, 2)
    0.00 (-1.00 to 3.50)
    1.75 (0.50 to 3.00)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    0.75 (-1.00 to 2.50)
        Change at Extension Month 12 (n = 1, 1)
    -1.00 (-1.00 to -1.00)
    4.50 (4.50 to 4.50)
        Change at Extension Month 15 (n = 1, 0)
    -1.00 (-1.00 to -1.00)
    99999 (99999 to 99999)
    Notes
    [284] - 99999 denotes data not available as there were no participants.
    [285] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    The Child-Pugh classification was a scoring system used for the classification of the severity of cirrhosis. It included three continuous variables (bilirubin, albumin, and INR) and two discrete variables (ascites and encephalopathy). Each variable was scored 1-3 with 3 indicating most severe derangement. The determination of child-pugh score ranged from 5 to 15. The higher the score, the sicker the participant. APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    12 [286]
    10 [287]
    Units: Score on a Scale
    median (inter-quartile range (Q1-Q3))
        Change at Day 1 (n = 12, 10)
    0.0 (-0.5 to 0.0)
    0.0 (0.0 to 0.0)
        Change at Week 6 (n = 9, 8)
    0.0 (-1.0 to 0.0)
    0.0 (-0.5 to 0.5)
        Change at Week 12 (n = 6, 7)
    -0.5 (-1.0 to 1.0)
    0.0 (-1.0 to 1.0)
        Change at Week 18 (n = 8, 8)
    0.0 (-1.0 to 0.0)
    -0.5 (-2.0 to 0.0)
        Change at Week 24 (n = 5, 5)
    -1.0 (-1.0 to 0.0)
    0.0 (-1.0 to 0.0)
        Change at Week 30 (n = 6, 6)
    -0.5 (-1.0 to 0.0)
    -1.0 (-2.0 to 0.0)
        Change at Week 36 (n = 6, 6)
    -1.0 (-1.0 to 0.0)
    -0.5 (-1.0 to 0.0)
        Change at Week 48 (n = 6, 6)
    -0.5 (-1.0 to 0.0)
    0.0 (-2.0 to 0.0)
        Change at Extension Month 3 (n = 6, 5)
    0.0 (-1.0 to 0.0)
    0.0 (-1.0 to 1.0)
        Change at Extension Month 6 (n = 3, 2)
    1.0 (-2.0 to 3.0)
    0.0 (0.0 to 0.0)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    0.0 (-1.0 to 1.0)
        Change at Extension Month 12 (n = 1, 1)
    1.0 (1.0 to 1.0)
    0.0 (0.0 to 0.0)
        Change at Extension Month 15 (n = 1, 0)
    1.0 (1.0 to 1.0)
    99999 (99999 to 99999)
    Notes
    [286] - 99999 denotes data not available as there were no participants.
    [287] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Number of Participants by Child-Pugh Score Component (Ascites Categories)

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    End point title
    		 Number of Participants by Child-Pugh Score Component (Ascites Categories)
    End point description
    Number of participants with Child-Pugh component - ascites categories of none, mild, and moderate-severe has been reported. The ascites categories were defined per investigator’s discretion. APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    12
    10
    Units: Participants
        Day 1: None (n =12, 10)
    6
    5
        Day 1: Mild (n =12, 10)
    5
    4
        Day 1: Moderate-Severe (n =12, 10)
    1
    1
        Week 6: None (n = 9, 9)
    7
    4
        Week 6: Mild (n = 9, 9)
    2
    5
        Week 6: Moderate-Severe (n = 9, 9)
    0
    0
        Week 12: None (n = 6, 7)
    4
    4
        Week 12: Mild (n = 6, 7)
    2
    3
        Week 12: Moderate-Severe (n = 6, 7)
    0
    0
        Week 18: None (n = 8, 8)
    6
    5
        Week 18: Mild (n = 8, 8)
    2
    3
        Week 18: Moderate-Severe (n = 8, 8)
    0
    0
        Week 24: None (n = 6, 6)
    6
    3
        Week 24: Mild (n = 6, 6)
    0
    3
        Week 24: Moderate-Severe (n = 6, 6)
    0
    0
        Week 30: None (n = 6, 6)
    6
    4
        Week 30: Mild (n = 6, 6)
    0
    2
        Week 30: Moderate-Severe (n = 6, 6)
    0
    0
        Week 36: None (n = 6, 6)
    6
    4
        Week 36: Mild (n = 6, 6)
    0
    2
        Week 36: Moderate-Severe (n = 6, 6)
    0
    0
        Week 48: None (n = 6, 6)
    6
    4
        Week 48: Mild (n = 6, 6)
    0
    1
        Week 48: Moderate-Severe (n = 6, 6)
    0
    1
        Extension Month 3: None (n = 6, 5)
    6
    2
        Extension Month 3: Mild (n = 6, 5)
    0
    1
        Extension Month 3: Moderate-Severe (n = 6, 5)
    0
    2
        Extension Month 6: None (n = 3, 2)
    1
    1
        Extension Month 6: Mild (n = 3, 2)
    1
    1
        Extension Month 6: Moderate-Severe (n = 3, 2)
    1
    0
        Extension Month 9: None (n = 0, 2)
    0
    1
        Extension Month 9: Mild (n = 0, 2)
    0
    1
        Extension Month 9: Moderate-Severe (n = 0, 2)
    0
    0
        Extension Month 12: None (n = 1, 1)
    0
    0
        Extension Month 12: Mild (n = 1, 1)
    1
    1
        Extension Month 12: Moderate-Severe (n = 1, 1)
    0
    0
        Extension Month 15: None (n = 1, 1)
    0
    0
        Extension Month 15: Mild (n = 1, 1)
    1
    1
        Extension Month 15: Moderate-Severe (n = 1, 1)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants by Child-Pugh Score Component (Prothrombin Time Categories)

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    End point title
    		 Number of Participants by Child-Pugh Score Component (Prothrombin Time Categories)
    End point description
    Number of participants with Child-Pugh component - prothrombin time (measured as INR) in categories of <1.7, 1.7 - 2.3, and >2.3 has been reported. APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    12
    10
    Units: Participants
        Day 1: <1.7 (n = 12, 10)
    12
    10
        Day 1: 1.7 - 2.3 (n = 12, 10)
    0
    0
        Day 1: >2.3 (n = 12, 10)
    0
    0
        Week 6: <1.7 (n = 9, 9)
    9
    9
        Week 6: 1.7 - 2.3 (n = 9, 9)
    0
    0
        Week 6: >2.3 (n = 9, 9)
    0
    0
        Week 12: <1.7 (n = 6, 7)
    6
    7
        Week 12: 1.7 - 2.3 (n = 6, 7)
    0
    0
        Week 12: >2.3 (n = 6, 7)
    0
    0
        Week 18: <1.7 (n = 8, 8)
    8
    8
        Week 18: 1.7 - 2.3 (n = 8, 8)
    0
    0
        Week 18: >2.3 (n = 8, 8)
    0
    0
        Week 24: <1.7 (n = 5, 5)
    4
    5
        Week 24: 1.7 - 2.3 (n = 5, 5)
    1
    0
        Week 24: >2.3 (n = 5, 5)
    0
    0
        Week 30: <1.7 (n = 6, 6)
    6
    6
        Week 30: 1.7 - 2.3 (n = 6, 6)
    0
    0
        Week 30: >2.3 (n = 6, 6)
    0
    0
        Week 36: <1.7 (n = 6, 6)
    6
    6
        Week 36: 1.7 - 2.3 (n = 6, 6)
    0
    0
        Week 36: >2.3 (n = 6, 6)
    0
    0
        Week 48: <1.7 (n = 6, 6)
    6
    6
        Week 48: 1.7 - 2.3 (n = 6, 6)
    0
    0
        Week 48: >2.3 (n = 6, 6)
    0
    0
        Extension Month 3: <1.7 (n = 6, 5)
    6
    5
        Extension Month 3: 1.7 - 2.3 (n = 6, 5)
    0
    0
        Extension Month 3: >2.3 (n = 6, 5)
    0
    0
        Extension Month 6: <1.7 (n = 3, 2)
    3
    2
        Extension Month 6: 1.7 - 2.3 (n = 3, 2)
    0
    0
        Extension Month 6: >2.3 (n = 3, 2)
    0
    0
        Extension Month 9: <1.7 (n = 0, 2)
    0
    2
        Extension Month 9: 1.7 - 2.3 (n = 0, 2)
    0
    0
        Extension Month 9: >2.3 (n = 0, 2)
    0
    0
        Extension Month 12: <1.7 (n = 1, 1)
    1
    1
        Extension Month 12: 1.7 - 2.3 (n = 1, 1)
    0
    0
        Extension Month 12: >2.3 (n = 1, 1)
    0
    0
        Extension Month 15: <1.7 (n = 1, 0)
    1
    0
        Extension Month 15: 1.7 - 2.3 (n = 1, 0)
    0
    0
        Extension Month 12: >2.3 (n = 1, 0)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants by Child-Pugh Score Component (Serum Albumin Categories)

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    End point title
    		 Number of Participants by Child-Pugh Score Component (Serum Albumin Categories)
    End point description
    Number of participants with Child-Pugh component - serum albumin levels in categories of >35 gram per liter (g/L), 28-35 g/L, or <28 g/L has been reported. APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    12
    10
    Units: Participants
        Day 1: >35 g/L (n = 12, 10)
    3
    4
        Day 1: 28-35 g/L (n = 12, 10)
    9
    4
        Day 1: <28 g/L (n = 12, 10)
    0
    2
        Week 6: >35 g/L (n = 9, 9)
    2
    4
        Week 6: 28-35 g/L (n = 9, 9)
    7
    3
        Week 6: <28 g/L (n = 9, 9)
    0
    2
        Week 12: >35 g/L (n = 6, 7)
    1
    3
        Week 12: 28-35 g/L (n = 6, 7)
    5
    3
        Week 12: <28 g/L (n = 6, 7)
    0
    1
        Week 18: >35 g/L (n = 8, 8)
    2
    5
        Week 18: 28-35 g/L (n = 8, 8)
    6
    3
        Week 18: <28 g/L (n = 8, 8)
    0
    0
        Week 24: >35 g/L (n = 6, 6)
    1
    3
        Week 24: 28-35 g/L (n = 6, 6)
    5
    3
        Week 24: <28 g/L (n = 6, 6)
    0
    0
        Week 30: >35 g/L (n = 6, 6)
    1
    3
        Week 30: 28-35 g/L (n = 6, 6)
    5
    3
        Week 30: <28 g/L (n = 6, 6)
    0
    0
        Week 36: >35 g/L (n = 6, 6)
    1
    2
        Week 36: 28-35 g/L (n = 6, 6)
    5
    4
        Week 36: <28 g/L (n = 6, 6)
    0
    0
        Week 48: >35 g/L (n = 6, 6)
    2
    3
        Week 48: 28-35 g/L (n = 6, 6)
    4
    3
        Week 48: <28 g/L (n = 6, 6)
    0
    0
        Extension Month 3: >35 g/L (n = 6, 5)
    1
    2
        Extension Month 3: 28-35 g/L (n = 6, 5)
    5
    3
        Extension Month 3: <28 g/L (n = 6, 5)
    0
    0
        Extension Month 6: >35 g/L (n = 3, 2)
    1
    1
        Extension Month 6: 28-35 g/L (n = 3, 2)
    2
    1
        Extension Month 6: <28 g/L (n = 3, 2)
    0
    0
        Extension Month 9: >35 g/L (n = 0, 2)
    0
    0
        Extension Month 9: 28-35 g/L (n = 0, 2)
    0
    2
        Extension Month 9: <28 g/L (n = 0, 2)
    0
    0
        Extension Month 12: >35 g/L (n = 1, 1)
    0
    1
        Extension Month 12: 28-35 g/L (n = 1, 1)
    1
    0
        Extension Month 12: <28 g/L (n = 1, 1)
    0
    0
        Extension Month 15: >35 g/L (n = 1, 1)
    0
    0
        Extension Month 15: 28-35 g/L (n = 1, 1)
    1
    1
        Extension Month 15: <28 g/L (n = 1, 1)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants by Child-Pugh Score Component (Total Bilirubin Categories)

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    End point title
    		 Number of Participants by Child-Pugh Score Component (Total Bilirubin Categories)
    End point description
    Number of participants with Child-Pugh component - total bilirubin levels in categories of <34 micromole per liter (μmol/ L), 34-50 μmol/L, and >50 μmol/L has been reported.
    End point type
    Secondary
    End point timeframe
    Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    12
    10
    Units: Participants
        Day 1: <34 μmol/L (n = 12, 10)
    3
    5
        Day 1: 34-50 μmol/L (n = 12, 10)
    5
    0
        Day 1: >50 μmol/L (n = 12, 10)
    4
    5
        Week 6: <34 μmol/L (n = 9, 8)
    4
    4
        Week 6: 34-50 μmol/L (n = 9, 8)
    1
    0
        Week 6: >50 μmol/L (n = 9, 8)
    4
    4
        Week 12: <34 μmol/L (n = 6, 7)
    2
    4
        Week 12: 34-50 μmol/L (n = 6, 7)
    3
    0
        Week 12: >50 μmol/L (n = 6, 7)
    1
    3
        Week 18: <34 μmol/L (n = 8, 8)
    2
    5
        Week 18: 34-50 μmol/L (n = 8, 8)
    3
    0
        Week 18: >50 μmol/L (n = 8, 8)
    3
    3
        Week 24: <34 μmol/L (n = 6, 6)
    2
    4
        Week 24: 34-50 μmol/L (n = 6, 6)
    3
    0
        Week 24: >50 μmol/L (n = 6, 6)
    1
    2
        Week 30: <34 μmol/L (n = 6, 6)
    3
    4
        Week 30: 34-50 μmol/L (n = 6, 6)
    1
    1
        Week 30: >50 μmol/L (n = 6, 6)
    2
    1
        Week 36: <34 μmol/L (n = 6, 6)
    3
    4
        Week 36: 34-50 μmol/L (n = 6, 6)
    1
    0
        Week 36: >50 μmol/L (n = 6, 6)
    2
    2
        Week 48: <34 μmol/L (n = 6, 6)
    2
    4
        Week 48: 34-50 μmol/L (n = 6, 6)
    1
    0
        Week 48: >50 μmol/L (n = 6, 6)
    3
    2
        Extension Month 3: <34 μmol/L (n = 6, 5)
    2
    3
        Extension Month 3: 34-50 μmol/L (n = 6, 5)
    1
    1
        Extension Month 3: >50 μmol/L (n = 6, 5)
    3
    1
        Extension Month 6: <34 μmol/L (n = 3, 2)
    1
    1
        Extension Month 6: 34-50 μmol/L (n = 3, 2)
    1
    0
        Extension Month 6: >50 μmol/L (n = 3, 2)
    1
    1
        Extension Month 9: <34 μmol/L (n = 0, 2)
    0
    1
        Extension Month 9: 34-50 μmol/L (n = 0, 2)
    0
    1
        Extension Month 9: >50 μmol/L (n = 0, 2)
    0
    0
        Extension Month 12: <34 μmol/L (n = 1, 1)
    0
    1
        Extension Month 12: 34-50 μmol/L (n = 1, 1)
    1
    0
        Extension Month 12: >50 μmol/L (n = 1, 1)
    0
    0
        Extension Month 15: <34 μmol/L (n = 1, 1)
    0
    1
        Extension Month 15: 34-50 μmol/L (n = 1, 1)
    1
    0
        Extension Month 15: >50 μmol/L (n = 1, 1)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants by Child-Pugh Score Component (Hepatic Encephalopathy Categories)

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    End point title
    		 Number of Participants by Child-Pugh Score Component (Hepatic Encephalopathy Categories)
    End point description
    Number of participants with Child-Pugh component - Hepatic encephalopathy in categories of Grade 0, Grade 1 or 2, and Grade 3 and 4 has been reported. Grade 0: normal consciousness, normal personality, normal neurological examination, normal electroencephalogram. Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles, per second (cps) waves. Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves. Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves. Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cps delta activity. APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    12
    10
    Units: Participants
        Day 1: Grade 0 (n = 12, 10)
    8
    8
        Day 1: Grade 1 or 2 (n = 12, 10)
    4
    2
        Day 1: Grade 3 or 4 (n = 12, 10)
    0
    0
        Week 6: Grade 0 (n = 9, 9)
    6
    6
        Week 6: Grade 1 or 2 (n = 9, 9)
    3
    3
        Week 6: Grade 3 or 4 (n = 9, 9)
    0
    0
        Week 12: Grade 0 (n = 6, 7)
    4
    5
        Week 12: Grade 1 or 2 (n = 6, 7)
    2
    2
        Week 12: Grade 3 or 4 (n = 6, 7)
    0
    0
        Week 18: Grade 0 (n = 8, 8)
    6
    7
        Week 18: Grade 1 or 2 (n = 8, 8)
    2
    1
        Week 18: Grade 3 or 4 (n = 8, 8)
    0
    0
        Week 24: Grade 0 (n = 6, 6)
    6
    5
        Week 24: Grade 1 or 2 (n = 6, 6)
    0
    1
        Week 24: Grade 3 or 4 (n = 6, 6)
    0
    0
        Week 30: Grade 0 (n = 6, 6)
    5
    5
        Week 30: Grade 1 or 2 (n = 6, 6)
    1
    1
        Week 30: Grade 3 or 4 (n = 6, 6)
    0
    0
        Week 36: Grade 0 (n = 6, 6)
    6
    5
        Week 36: Grade 1 or 2 (n = 6, 6)
    0
    1
        Week 36: Grade 3 or 4 (n = 6, 6)
    0
    0
        Week 48: Grade 0 (n = 6, 6)
    5
    5
        Week 48: Grade 1 or 2 (n = 6, 6)
    1
    1
        Week 48: Grade 3 or 4 (n = 6, 6)
    0
    0
        Extension Month 3: Grade 0 (n = 6, 5)
    5
    4
        Extension Month 3: Grade 1 or 2 (n = 6, 5)
    1
    1
        Extension Month 3: Grade 3 or 4 (n = 6, 5)
    0
    0
        Extension Month 6: Grade 0 (n = 3, 2)
    3
    1
        Extension Month 6: Grade 1 or 2 (n = 3, 2)
    0
    1
        Extension Month 6: Grade 3 or 4 (n = 3, 2)
    0
    0
        Extension Month 9: Grade 0 (n = 0, 2)
    0
    1
        Extension Month 9: Grade 1 or 2 (n = 0, 2)
    0
    1
        Extension Month 9: Grade 3 or 4 (n = 0, 2)
    0
    0
        Extension Month 12: Grade 0 (n = 1, 1)
    1
    0
        Extension Month 12: Grade 1 or 2 (n = 1, 1)
    0
    1
        Extension Month 12: Grade 3 or 4 (n = 1, 1)
    0
    0
        Extension Month 15: Grade 0 (n = 1, 1)
    1
    0
        Extension Month 15: Grade 1 or 2 (n = 1, 1)
    0
    1
        Extension Month 15: Grade 3 or 4 (n = 1, 1)
    0
    0
    No statistical analyses for this end point

    Secondary: Change From Baseline in Total Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Total Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11 [288]
    10
    Units: μmol/L
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    0.86 (-13.0 to 6.50)
    -3.25 (-4.00 to 24.00)
        Change at Week 6 (n = 9, 8)
    3.00 (-1.50 to 5.99)
    -2.14 (-3.43 to 26.75)
        Change at Week 12 (n = 7, 7)
    0.86 (-4.28 to 9.00)
    -1.71 (-6.00 to 17.96)
        Change at Week 18 (n = 8, 8)
    1.08 (-4.70 to 16.05)
    -4.03 (-9.00 to 3.21)
        Change at Week 24 (n = 5, 7)
    2.67 (-1.50 to 20.40)
    -3.50 (-10.00 to 1.71)
        Change at Week 30 (n = 6, 6)
    2.08 (-2.57 to 31.34)
    -8.49 (-9.00 to -5.50)
        Change at Week 36 (n = 6, 6)
    4.25 (-11.12 to 9.67)
    -3.53 (-7.00 to 3.42)
        Change at Week 42 (n = 6, 7)
    6.58 (-7.70 to 12.00)
    1.71 (-2.85 to 6.00)
        Change at Week 48 (n = 6, 6)
    6.25 (-2.57 to 23.67)
    -3.75 (-6.27 to -0.57)
        Change at Extension Month 3 (n = 6, 5)
    2.25 (0.86 to 60.67)
    0.50 (-16.00 to 0.57)
        Change at Extension Month 6 (n = 3, 2)
    -1.50 (-12.83 to 21.38)
    -0.22 (-1.00 to 0.57)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    -7.86 (-18.00 to 2.28)
        Change at Extension Month 12 (n = 1, 1)
    -14.54 (-14.54 to -14.54)
    9.12 (9.12 to 9.12)
        Change at Extension Month 15 (n = 1, 1)
    -12.83 (-12.83 to -12.83)
    24.51 (24.51 to 24.51)
    Notes
    [288] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11 [289]
    10
    Units: μmol/L
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    0.00 (-6.04 to 1.50)
    -1.07 (-1.50 to 15.00)
        Change at Week 6 (n = 8, 8)
    2.53 (0.00 to 7.25)
    -1.32 (-4.61 to 18.50)
        Change at Week 12 (n = 7, 7)
    4.28 (0.00 to 12.50)
    -1.14 (-3.00 to 1.71)
        Change at Week 18 (n = 8, 8)
    2.99 (0.50 to 14.20)
    -1.82 (-3.25 to 2.00)
        Change at Week 24 (n = 5, 6)
    1.00 (-1.00 to 15.00)
    -1.75 (-2.85 to 0.00)
        Change at Week 30 (n = 6, 5)
    0.93 (-1.00 to 6.10)
    -2.50 (-4.00 to -1.71)
        Change at Week 36 (n = 6, 6)
    0.00 (-4.28 to 3.37)
    -1.57 (-2.50 to 0.00)
        Change at Week 42 (n = 6, 7)
    2.50 (-2.57 to 9.37)
    -1.71 (-2.66 to 1.50)
        Change at Week 48 (n = 6, 6)
    3.61 (-1.00 to 15.00)
    -2.36 (-6.08 to -1.14)
        Change at Extension Month 3 (n = 5, 5)
    3.37 (0.00 to 4.28)
    -2.00 (-15.00 to 1.50)
        Change at Extension Month 6 (n = 3, 2)
    0.00 (-5.99 to 19.67)
    -1.00 (-6.00 to 3.99)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    -3.79 (-15.00 to 7.41)
        Change at Extension Month 12 (n = 1, 1)
    -9.41 (-9.41 to -9.41)
    7.41 (7.41 to 7.41)
        Change at Extension Month 15 (n = 1, 1)
    -5.99 (-5.99 to -5.99)
    12.54 (12.54 to 12.54)
    Notes
    [289] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11 [290]
    10
    Units: unit per liter (U/ L)
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    -21.0 (-48.0 to 6.0)
    -9.0 (-48.0 to 0.0)
        Change at Week 6 (n = 9, 9)
    -7.0 (-22.0 to 19.0)
    5.0 (-12.0 to 15.0)
        Change at Week 12 (n = 7, 7)
    -1.0 (-54.0 to 12.0)
    -17.0 (-32.0 to 6.0)
        Change at Week 18 (n = 8, 8)
    -20.5 (-35.5 to 16.5)
    -4.5 (-37.5 to 1.5)
        Change at Week 24 (n = 5, 7)
    -30.0 (-66.0 to 16.0)
    -5.0 (-100.0 to 4.0)
        Change at Week 30 (n = 6, 6)
    -34.5 (-76.0 to -19.0)
    -20.0 (-33.0 to -7.0)
        Change at Week 36 (n = 6, 8)
    -26.0 (-64.0 to -6.0)
    -4.0 (-89.5 to 4.0)
        Change at Week 42 (n = 6, 7)
    -24.0 (-45.0 to -17.0)
    5.0 (-87.0 to 9.0)
        Change at Week 48 (n = 6, 5)
    -29.0 (-63.0 to -17.0)
    8.0 (-3.0 to 13.0)
        Change at Extension Month 3 (n = 6, 5)
    -24.0 (-48.0 to -7.0)
    10.0 (-14.0 to 26.0)
        Change at Extension Month 6 (n = 3, 2)
    6.0 (-33.0 to 7.0)
    -46.0 (-133.0 to 41.0)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    -66.5 (-148.0 to 15.0)
        Change at Extension Month 12 (n = 1, 1)
    -72.0 (-72.0 to -72.0)
    122.0 (122.0 to 122.0)
        Change at Extension Month 15 (n = 1, 1)
    -83.0 (-83.0 to -83.0)
    10.0 (10.0 to 10.0)
    Notes
    [290] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11 [291]
    10
    Units: U/L
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    -5.0 (-9.0 to -1.0)
    -2.0 (-9.0 to 1.0)
        Change at Week 6 (n = 9, 8)
    -5.0 (-9.0 to 1.0)
    2.5 (-1.0 to 12.5)
        Change at Week 12 (n = 7, 7)
    1.0 (-9.0 to 5.0)
    10.0 (1.0 to 19.0)
        Change at Week 18 (n = 8, 8)
    -6.5 (-12.5 to -3.5)
    -0.5 (-5.0 to 1.5)
        Change at Week 24 (n = 5, 6)
    -4.0 (-5.0 to 4.0)
    -4.0 (-8.0 to 3.0)
        Change at Week 30 (n = 6, 6)
    -6.0 (-12.0 to 3.0)
    1.5 (-2.0 to 3.0)
        Change at Week 36 (n = 6, 7)
    11.5 (-6.0 to 24.0)
    -3.0 (-5.0 to 5.0)
        Change at Week 42 (n = 6, 7)
    -9.0 (-12.0 to -3.0)
    -1.0 (-6.0 to 1.0)
        Change at Week 48 (n = 6, 6)
    -6.0 (-7.0 to -2.0)
    1.0 (-1.0 to 2.0)
        Change at Extension Month 3 (n = 6, 5)
    -8.0 (-12.0 to -3.0)
    -1.0 (-7.0 to 7.0)
        Change at Extension Month 6 (n = 3, 2)
    -12.0 (-27.0 to -1.0)
    -1.5 (-6.0 to 3.0)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    -6.0 (-11.0 to -1.0)
        Change at Extension Month 12 (n = 1, 1)
    -34.0 (-34.0 to -34.0)
    -2.0 (-2.0 to -2.0)
        Change at Extension Month 15 (n = 1, 1)
    -32.0 (-32.0 to -32.0)
    1.0 (1.0 to 1.0)
    Notes
    [291] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11 [292]
    10
    Units: U/L
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    -4.0 (-11.0 to 3.0)
    -1.0 (-13.0 to 6.0)
        Change at Week 6 (n = 8, 8)
    -4.0 (-12.0 to 0.5)
    10.5 (-3.5 to 23.5)
        Change at Week 12 (n = 7, 7)
    0.0 (-5.0 to 19.0)
    18.0 (-3.0 to 29.0)
        Change at Week 18 (n = 8, 8)
    -1.5 (-7.5 to 5.5)
    -5.0 (-10.5 to 4.5)
        Change at Week 24 (n = 5, 6)
    -7.0 (-13.0 to -2.0)
    -2.0 (-7.0 to 1.0)
        Change at Week 30 (n = 6, 6)
    -10.0 (-12.0 to -3.0)
    1.0 (-2.0 to 9.0)
        Change at Week 36 (n = 6, 7)
    19.5 (-10.0 to 34.0)
    2.0 (-4.0 to 15.0)
        Change at Week 42 (n = 6, 7)
    -3.5 (-14.0 to 8.0)
    1.0 (-2.0 to 39.0)
        Change at Week 48 (n = 6, 6)
    -12.0 (-22.0 to 7.0)
    0.5 (-15.0 to 20.0)
        Change at Extension Month 3 (n = 6, 5)
    -6.5 (-11.0 to 6.0)
    -12.0 (-15.0 to 6.0)
        Change at Extension Month 6 (n = 3, 2)
    -16.0 (-32.0 to 1.0)
    -0.5 (-21.0 to 20.0)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    -8.5 (-33.0 to 16.0)
        Change at Extension Month 12 (n = 1, 1)
    -33.0 (-33.0 to -33.0)
    19.0 (19.0 to 19.0)
        Change at Extension Month 15 (n = 1, 1)
    -34.0 (-34.0 to -34.0)
    16.0 (16.0 to 16.0)
    Notes
    [292] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    10 [293]
    10
    Units: U/L
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 10, 10)
    -12.5 (-27.0 to -2.0)
    -13.5 (-54.0 to -1.0)
        Change at Week 6 (n = 9, 9)
    -11.0 (-28.0 to -3.0)
    0.0 (-31.0 to 4.0)
        Change at Week 12 (n = 7, 7)
    -13.0 (-32.0 to -3.0)
    -2.0 (-44.0 to 7.0)
        Change at Week 18 (n = 8, 8)
    -9.5 (-28.0 to -0.5)
    -3.5 (-38.5 to 1.5)
        Change at Week 24 (n = 5, 7)
    8.0 (-37.0 to 25.0)
    -14.0 (-70.0 to -5.0)
        Change at Week 30 (n = 5, 6)
    -9.0 (-22.0 to -5.0)
    -12.5 (-27.0 to 5.0)
        Change at Week 36 (n = 6, 8)
    -5.5 (-12.0 to 24.0)
    -10.5 (-90.0 to 4.5)
        Change at Week 42 (n = 6, 7)
    -12.0 (-26.0 to 5.0)
    -4.0 (-154.0 to 17.0)
        Change at Week 48 (n = 6, 6)
    -9.0 (-21.0 to -6.0)
    -15.0 (-112.0 to 9.0)
        Change at Extension Month 3 (n = 6, 5)
    -9.5 (-48.0 to 1.0)
    9.0 (-14.0 to 22.0)
        Change at Extension Month 6 (n = 3, 2)
    -10.0 (-35.0 to -9.0)
    -58.5 (-137.0 to 20.0)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    -57.0 (-128.0 to 14.0)
        Change at Extension Month 12 (n = 1, 1)
    -74.0 (-74.0 to -74.0)
    8.0 (8.0 to 8.0)
        Change at Extension Month 15 (n = 1, 1)
    -63.0 (-63.0 to -63.0)
    2.0 (2.0 to 2.0)
    Notes
    [293] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11
    10 [294]
    Units: INR
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    0.00 (0.00 to 0.10)
    0.00 (0.00 to 0.10)
        Change at Week 6 (n = 9, 9)
    0.00 (-0.03 to 0.00)
    0.00 (-0.05 to 0.00)
        Change at Week 12 (n = 6, 7)
    0.08 (0.00 to 0.15)
    -0.05 (-0.10 to 0.00)
        Change at Week 18 (n = 8, 8)
    0.09 (0.00 to 0.10)
    -0.05 (-0.13 to 0.05)
        Change at Week 24 (n = 4, 5)
    0.03 (-0.02 to 0.08)
    -0.05 (-0.10 to 0.05)
        Change at Week 30 (n = 6, 6)
    0.03 (-0.03 to 0.10)
    0.00 (-0.10 to 0.00)
        Change at Week 36 (n = 6, 8)
    0.05 (0.00 to 0.10)
    -0.10 (-0.18 to 0.03)
        Change at Week 42 (n = 6, 7)
    0.05 (0.00 to 0.07)
    0.00 (-0.10 to 0.05)
        Change at Week 48 (n = 6, 5)
    0.00 (-0.03 to 0.05)
    -0.10 (-0.15 to 0.00)
        Change at Extension Month 3 (n = 6, 5)
    0.06 (0.00 to 0.10)
    -0.10 (-0.10 to -0.10)
        Change at Extension Month 6 (n = 3, 2)
    0.05 (-0.10 to 0.15)
    -0.05 (-0.10 to 0.00)
        Change at Extension Month 9 (n = 1, 2)
    0.15 (0.15 to 0.15)
    0.00 (0.00 to 0.00)
        Change at Extension Month 12 (n = 1, 1)
    0.05 (0.05 to 0.05)
    0.10 (0.10 to 0.10)
        Change at Extension Month 15 (n = 1, 0)
    0.05 (0.05 to 0.05)
    99999 (99999 to 99999)
    Notes
    [294] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    11 [295]
    10
    Units: μmol/L
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 11, 10)
    0.884 (-3.000 to 5.000)
    -0.308 (-2.000 to 1.768)
        Change at Week 6 (n = 9, 9)
    5.000 (0.388 to 5.746)
    0.884 (-1.000 to 4.000)
        Change at Week 12 (n = 7, 7)
    -0.496 (-4.000 to 13.500)
    2.500 (-1.000 to 5.000)
        Change at Week 18 (n = 8, 8)
    -2.431 (-4.958 to 7.250)
    0.942 (-6.170 to 5.036)
        Change at Week 24 (n = 5, 7)
    -1.000 (-4.000 to -0.496)
    -2.652 (-11.492 to 5.000)
        Change at Week 30 (n = 6, 6)
    -0.663 (-4.032 to 1.768)
    -2.250 (-6.188 to 3.000)
        Change at Week 36 (n = 6, 8)
    1.500 (-1.326 to 7.000)
    2.466 (-1.960 to 33.586)
        Change at Week 42 (n = 6, 7)
    2.000 (-1.326 to 4.000)
    6.236 (-2.652 to 28.000)
        Change at Week 48 (n = 6, 6)
    2.221 (-3.536 to 6.000)
    0.466 (-3.000 to 20.000)
        Change at Extension Month 3 (n = 6, 5)
    3.884 (0.000 to 6.630)
    0.000 (-1.500 to 12.000)
        Change at Extension Month 6 (n = 3, 2)
    2.652 (-4.000 to 12.818)
    4.648 (-7.500 to 16.796)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    15.068 (4.500 to 25.636)
        Change at Extension Month 12 (n = 1, 1)
    10.608 (10.608 to 10.608)
    27.404 (27.404 to 27.404)
        Change at Extension Month 15 (n = 1, 1)
    4.420 (4.420 to 4.420)
    29.172 (29.172 to 29.172)
    Notes
    [295] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    10 [296]
    10
    Units: g/L
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 10, 10)
    -2.25 (-2.50 to -1.00)
    -0.50 (-1.70 to 0.00)
        Change at Week 6 (n = 9, 9)
    -1.00 (-3.00 to 0.00)
    0.00 (-1.00 to 1.30)
        Change at Week 12 (n = 7, 7)
    -2.00 (-4.00 to -1.50)
    -0.70 (-1.00 to 1.50)
        Change at Week 18 (n = 8, 8)
    -4.25 (-5.00 to -1.50)
    0.00 (-1.60 to 0.50)
        Change at Week 24 (n = 5, 7)
    -2.50 (-4.00 to -1.00)
    -2.50 (-2.70 to 1.00)
        Change at Week 30 (n = 6, 6)
    -2.50 (-4.00 to -2.00)
    0.15 (-1.50 to 1.00)
        Change at Week 36 (n = 6, 8)
    -2.00 (-3.00 to -2.00)
    0.50 (-2.35 to 2.25)
        Change at Week 42 (n = 6, 7)
    -1.25 (-4.00 to 0.00)
    -0.70 (-1.00 to 2.00)
        Change at Week 48 (n = 6, 6)
    -0.50 (-2.00 to 1.00)
    0.50 (-4.70 to 1.00)
        Change at Extension Month 3 (n = 6, 5)
    -2.50 (-3.00 to -1.00)
    1.00 (-2.70 to 2.50)
        Change at Extension Month 6 (n = 3, 2)
    -2.00 (-3.00 to -1.00)
    -0.35 (-1.70 to 1.00)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    -1.35 (-3.70 to 1.00)
        Change at Extension Month 12 (n = 1, 1)
    -1.00 (-1.00 to -1.00)
    -2.70 (-2.70 to -2.70)
        Change at Extension Month 15 (n = 1, 1)
    -1.00 (-1.00 to -1.00)
    -11.70 (-11.70 to -11.70)
    Notes
    [296] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Platelets at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

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    End point title
    		 Change From Baseline in Platelets at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    10 [297]
    9
    Units: 10^9/L
    median (inter-quartile range (Q1-Q3))
        Change at Week 3 (n = 10, 9)
    -6.2 (-21.0 to -3.0)
    -7.5 (-12.0 to 8.5)
        Change at Week 6 (n = 8, 6)
    -12.0 (-28.8 to -2.3)
    15.0 (1.0 to 26.5)
        Change at Week 12 (n = 6, 5)
    -10.5 (-31.0 to 7.5)
    -15.0 (-15.0 to -1.5)
        Change at Week 18 (n = 6, 7)
    -15.0 (-21.9 to -8.5)
    7.5 (-10.0 to 38.5)
        Change at Week 24 (n = 5, 6)
    4.5 (-14.4 to 17.0)
    -1.5 (-25.0 to 25.5)
        Change at Week 30 (n = 6, 5)
    -11.4 (-23.5 to 15.0)
    -5.5 (-9.0 to 6.5)
        Change at Week 36 (n = 6, 6)
    -16.5 (-20.5 to -12.0)
    9.8 (-6.5 to 39.5)
        Change at Week 42 (n = 6, 6)
    -16.2 (-37.5 to -10.0)
    9.0 (6.5 to 11.0)
        Change at Week 48 (n = 5, 5)
    4.0 (-41.5 to 23.0)
    -9.0 (-11.5 to 14.5)
        Change at Extension Month 3 (n = 6, 5)
    -5.0 (-24.0 to 16.5)
    -11.5 (-24.0 to -8.5)
        Change at Extension Month 6 (n = 3, 1)
    48.5 (14.0 to 78.0)
    -0.5 (-0.5 to -0.5)
        Change at Extension Month 9 (n = 0, 2)
    99999 (99999 to 99999)
    -4.5 (-5.5 to -3.5)
        Change at Extension Month 12 (n = 1, 1)
    -2.0 (-2.0 to -2.0)
    -3.5 (-3.5 to -3.5)
        Change at Extension Month 15 (n = 1, 1)
    -9.0 (-9.0 to -9.0)
    -22.5 (-22.5 to -22.5)
    Notes
    [297] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

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    End point title
    		 Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
    End point description
    Total bile acids (micromole [μM]) = total ursodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total cholic acid (unconjugated, glyco-conjugate, tauroconjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM. APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 6, 12, 18, 24, 30, 36, 48; and Extension Month 3
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    7 [298]
    8
    Units: μM
    median (inter-quartile range (Q1-Q3))
        Change at Week 6 (n = 7, 8)
    16.3 (-7.68 to 37.4)
    8.09 (-15.9 to 37.1)
        Change at Week 12 (n = 6, 6)
    0.863 (-21.0 to 88.4)
    5.55 (-58.4 to 13.7)
        Change at Week 18 (n = 7, 7)
    17.7 (-56.0 to 160)
    12.8 (-169 to 36.0)
        Change at Week 24 (n = 4, 4)
    3.29 (-76.6 to 30.6)
    -3.14 (-14.5 to 21.3)
        Change at Week 30 (n = 4, 6)
    26.0 (-56.0 to 98.5)
    16.1 (-7.06 to 38.7)
        Change at Week 36 (n = 5, 8)
    -15.2 (-79.4 to 10.0)
    -1.54 (-22.9 to 24.6)
        Change at Week 48 (n = 4, 5)
    63.2 (16.7 to 132)
    0.876 (-4.07 to 19.5)
        Change at Extension Month 3 (n = 0, 1)
    99999 (99999 to 99999)
    -32.9 (-32.9 to -32.9)
    Notes
    [298] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

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    End point title
    		 Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
    End point description
    Total endogenous bile acids (μM) = total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total cholic acid (unconjugated, glycoconjugate, tauro-conjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM. APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    7 [299]
    9
    Units: μM
    median (inter-quartile range (Q1-Q3))
        Change at Week 6 (n = 7, 9)
    -4.98 (-6.88 to 36.2)
    3.58 (-5.64 to 14.0)
        Change at Week 12 (n = 6, 6)
    -3.97 (-13.3 to 63.9)
    1.46 (-5.43 to 4.81)
        Change at Week 18 (n = 7, 7)
    -5.00 (-20.2 to 51.0)
    3.98 (-18.3 to 7.21)
        Change at Week 24 (n = 4, 6)
    -6.76 (-18.5 to -1.25)
    3.18 (-2.53 to 15.2)
        Change at Week 30 (n = 5, 6)
    6.74 (-6.22 to 7.44)
    1.47 (-3.87 to 13.6)
        Change at Week 36 (n = 6, 8)
    -5.74 (-24.9 to -0.576)
    -2.69 (-14.4 to 9.66)
        Change at Week 48 (n = 6, 6)
    10.9 (6.32 to 19.8)
    4.18 (-2.08 to 9.82)
        Change at Extension Month 3 (n = 0, 1)
    99999 (99999 to 99999)
    -9.57 (-9.57 to -9.57)
    Notes
    [299] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in 7α-hydroxy-4-cholesten-3-one (C4) at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

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    End point title
    		 Change From Baseline in 7α-hydroxy-4-cholesten-3-one (C4) at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    8 [300]
    9
    Units: ng/mL
    median (inter-quartile range (Q1-Q3))
        Change at Week 6 (n = 8, 9)
    0.0990 (-0.0445 to 0.296)
    0.0770 (-0.110 to 0.450)
        Change at Week 12 (n = 6, 7)
    -0.0275 (-0.0690 to 0.156)
    -0.289 (-1.31 to 0.0100)
        Change at Week 18 (n = 7, 8)
    -0.0470 (-0.278 to 0.205)
    -0.267 (-0.965 to 8.05)
        Change at Week 24 (n = 4, 6)
    -0.00100 (-0.00700 to 0.692)
    -0.141 (-1.67 to 1.07)
        Change at Week 30 (n = 5, 6)
    0.0890 (0.0500 to 0.355)
    -0.386 (-1.77 to 2.50)
        Change at Week 36 (n = 6, 8)
    0.118 (-0.104 to 0.240)
    -0.476 (-3.53 to 5.41)
        Change at Week 48 (n = 6, 6)
    -0.170 (-0.491 to -0.0140)
    -0.510 (-1.83 to 5.20)
        Change at Extension Month 3 (n = 0, 1)
    99999 (99999 to 99999)
    1.36 (1.36 to 1.36)
    Notes
    [300] - 99999 denotes data not available as there were no participants.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

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    End point title
    		 Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
    End point description
    APD: Participants in the ITT population with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
    End point values
    		 Placebo Obeticholic Acid (OCA)
    Number of subjects analysed
    8
    9
    Units: picograms per milliliter (pg/mL)
    median (inter-quartile range (Q1-Q3))
        Change at Week 6 (n = 8, 9)
    -50.7 (-142 to 33.0)
    26.0 (4.50 to 101)
        Change at Week 12 (n = 6, 7)
    -14.0 (-220 to 19.0)
    119 (-25.6 to 174)
        Change at Week 18 (n = 7, 8)
    -57.0 (-118 to 40.0)
    136 (-28.3 to 298)
        Change at Week 24 (n = 4, 6)
    -33.0 (-152 to 402)
    16.6 (-24.0 to 219)
        Change at Week 30 (n = 5, 6)
    -83.0 (-123 to 43.0)
    142 (-45.0 to 168)
        Change at Week 36 (n = 6, 8)
    26.0 (-34.0 to 102)
    15.0 (-97.4 to 201)
        Change at Week 48 (n = 6, 6)
    -28.5 (-161 to 84.5)
    69.6 (8.00 to 145)
        Change at Extension Month 3 (n = 1, 1)
    -117 (-117 to -117)
    0 (0 to 0)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to approximately 3 years
    Adverse event reporting additional description
    The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Obeticholic Acid (OCA)
    Reporting group description
    		 Participants initiated treatment with OCA 5 mg tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks. Participants, who had completed their 48 Week treatment, could continue the treatment until all randomized participants had completed their 48 Week treatment period and the database for that period was locked (total duration: approximately up to 3 years).

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks. Participants, who had completed their 48 Week treatment, could continue the treatment until all randomized participants had completed their 48 Week treatment period and the database for that period was locked (total duration: approximately up to 3 years).

    Serious adverse events
    		 Obeticholic Acid (OCA) Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 10 (70.00%)
    9 / 12 (75.00%)
         number of deaths (all causes)
    2
    2
         number of deaths resulting from adverse events
    Vascular disorders
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Surgical and medical procedures
    Liver transplant
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Blood and lymphatic system disorders
    Pancytopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    3 / 10 (30.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonia aspiration
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrothorax
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Obeticholic Acid (OCA) Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 10 (100.00%)
    10 / 12 (83.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pituitary tumour benign
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Peripheral coldness
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Haematoma
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    2
    Haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    3
    1
    Chest discomfort
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Disease progression
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 12 (33.33%)
         occurrences all number
    1
    4
    Asthenia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    4
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Breast pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Cough
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Haemoptysis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Blood urea increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Cardiac murmur
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Tooth fracture
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 12 (16.67%)
         occurrences all number
    1
    2
    Joint injury
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Angina pectoris
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Palpitations
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    1
    Burning sensation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Balance disorder
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Encephalopathy
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Hypoaesthesia
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Neuralgia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Memory impairment
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 10 (30.00%)
    1 / 12 (8.33%)
         occurrences all number
    3
    1
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Vitreous floaters
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    6 / 10 (60.00%)
    4 / 12 (33.33%)
         occurrences all number
    6
    4
    Abdominal distension
         subjects affected / exposed
    2 / 10 (20.00%)
    3 / 12 (25.00%)
         occurrences all number
    2
    3
    Diarrhoea
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    3
    2
    Nausea
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 12 (16.67%)
         occurrences all number
    3
    3
    Vomiting
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    4
    1
    Abdominal discomfort
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
         occurrences all number
    3
    1
    Dyspepsia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Flatulence
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Frequent bowel movements
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Haematemesis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Melaena
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain lower
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    Dry mouth
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastric antral vascular ectasia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastric polyps
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Toothache
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Large intestine polyp
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Portal hypertensive gastropathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Varices oesophageal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Abdominal Pain
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    3
    1
    Hepatobiliary disorders
    Portal vein thrombosis
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    1
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    3 / 10 (30.00%)
    2 / 12 (16.67%)
         occurrences all number
    4
    4
    Skin mass
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Palmar erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    3
    3
    Endocrine disorders
    Thyroid mass
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    Arthralgia
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    3
    Limb mass
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Back pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    2
    Muscle spasms
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Urinary tract infection
         subjects affected / exposed
    3 / 10 (30.00%)
    2 / 12 (16.67%)
         occurrences all number
    3
    2
    Oesophageal candidiasis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Cytomegalovirus infection reactivation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Cellulitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Peritonitis bacterial
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Ear infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Fungal infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Skin infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Dehydration
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 May 2017
    The changes in Version 2 were incorporated based on Food and Drug Administration (FDA) review of Version 1 of the protocol: • Background information was included to estimate the exposure difference between healthy subjects and subjects with moderate hepatic impairment to support the rationale for dose selection • Additional PK sampling times were added to adequately characterize the PK of OCA and its active metabolites at steady state in subjects with moderate and severe impairment when dosing weekly to biweekly • The period between screening and Day 1 was extended to at least 14 days to establish a baseline for serum biomarkers with at least two samples two weeks apart • The Week 3 contact Visit by email/telephone was changed to a Safety Visit to assess evidence of early hepatotoxicity • Guidelines were added to assess subjects for evidence of hepatotoxicity at each visit
    04 Jan 2018
    • The Introduction was revised to highlight the need for close monitoring specifically in subjects with clinical evidence of hepatic decompensation and other complications due to advanced cirrhosis. • Dosing regimens were updated to modify dosing to one regimen for subjects with moderate and severe hepatic impairment [e.g., same for child-pugh B and child-pugh C ], not to exceed 10 mg twice weekly, to align with label dosing guidelines. Titration was then only based on tolerability and not CP score. • Reference to an option for open-label treatment was removed. An open-label extension was to be considered only after review of blinded safety and PK data from the double-blind treatment period. • Protocol was updated with discontinuation criteria for decompensation events and biochemical thresholds. A plan for monitoring and drug-induced liver injury algorithm was included to ensure careful monitoring and drug interruption/discontinuation. Analysis of decompensation events as adverse events of interest was added. Additionally, “Close Observation” per FDA Guidance for Industry on Drug Induced Liver Injury (DILI) was clearly defined in the protocol to ensure that subjects who experienced a potential DILI underwent a full evaluation. • Guidance was added that subjects should have been instructed to contact the site promptly upon awareness if they developed signs and symptoms of potential hepatic decompensation. • Guidance was added that the Investigator should have contacted the study Medical Monitor upon awareness when any signs and symptoms of hepatic decompensation were observed in any subject. • Guidance was added for monitoring amylase and lipase levels in subjects with suspected acute pancreatitis. • Gallbladder assessments were added at Screening or Day 1.
    15 Feb 2019
    • Updated clinical development data based on IB Version 18 (31 Jan 2019). • Exclusion criteria were updated to mitigate the inclusion of subjects who may have been pregnant or breastfeeding as an additional safety precaution or who had a known history of human immunodeficiency syndrome infection. • Exclusion criteria and prohibited medications sections were updated to prevent the concomitant use of fibrates and OCA. The primary objective of this study was to characterize the PK of OCA in subjects with PBC and mild to severe hepatic impairment. The drug-drug interactions of OCA with fibrates were not yet fully characterized in any population and were being restricted in this study as an additional safety precaution until data were available in a less advanced population.
    19 May 2020
    • Addendum was issued to multiple countries to describe the requirements and processes under which subjects who were unable to return to study sites during the COVID-19 pandemic may have completed protocol specified assessments and continued to receive investigational product until in-person site visits could resume.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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