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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

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    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
         Consent withdrawn by subject
    1
    1
         Physician decision
    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