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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03633227




Registration number
NCT03633227
Ethics application status
Date submitted
8/04/2018
Date registered
16/08/2018
Date last updated
6/09/2022

Titles & IDs
Public title
Study of Obeticholic Acid (OCA) Evaluating Pharmacokinetics and Safety in Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment
Scientific title
A Phase 4, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Pharmacokinetics and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment
Secondary ID [1] 0 0
747-401
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver Cirrhosis, Biliary 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 0 0 0 0
Other infectious diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obeticholic Acid (OCA)
Treatment: Drugs - Placebo

Experimental: Obeticholic Acid (OCA) - Participants will initiate treatment with OCA 5 milligrams (mg) tablets orally once weekly. At Week 12, if there are no safety concerns, the dose will be up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose will be considered. At each titration visit, the participants will start the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration will be OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration will be 48-weeks. Participants, who complete their 48-week treatment, can continue the treatment until all randomized participants complete their 48-week treatment period and the database for that period is locked (total duration: approximately up to 3 years).

Placebo comparator: Placebo - Participants will receive OCA matching placebo orally once weekly or twice weekly for the duration of at least 48-weeks. Participants, who complete their 48-week treatment, can continue the treatment until all randomized participants complete their 48-week treatment period and the database for that period is locked (total duration: approximately up to 3 years).


Treatment: Drugs: Obeticholic Acid (OCA)
OCA will be administered per dose and schedule specified in the arm description.

Treatment: Drugs: Placebo
OCA matching placebo will be administered per the schedule specified in the arm description.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Observed Concentration (Cmax) of Total OCA at Week 12
Timepoint [1] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [2] 0 0
Time to Maximum Concentration (Tmax) of Total OCA at Week 12
Timepoint [2] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [3] 0 0
Trough Concentration (Ctrough) of Total OCA at Week 12
Timepoint [3] 0 0
24 hours post-dose at Week 12
Primary outcome [4] 0 0
Area Under the Concentration Versus Time Curve From Zero Time to 24 Hours (AUC0-24h) of Total OCA at Week 12
Timepoint [4] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [5] 0 0
Cmax of Total OCA at Week 18
Timepoint [5] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [6] 0 0
Tmax of Total OCA at Week 18
Timepoint [6] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [7] 0 0
Ctrough of Total OCA at Week 18
Timepoint [7] 0 0
24 hours post-dose at Week 18
Primary outcome [8] 0 0
AUC0-24h of Total OCA at Week 18
Timepoint [8] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [9] 0 0
Cmax of Total OCA at Week 24
Timepoint [9] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [10] 0 0
Tmax of Total OCA at Week 24
Timepoint [10] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [11] 0 0
Ctrough of Total OCA at Week 24
Timepoint [11] 0 0
24 hours post-dose at Week 24
Primary outcome [12] 0 0
AUC0-24h of Total OCA at Week 24
Timepoint [12] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [13] 0 0
Cmax of Total OCA at Week 30
Timepoint [13] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [14] 0 0
Tmax of Total OCA at Week 30
Timepoint [14] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [15] 0 0
Ctrough of Total OCA at Week 30
Timepoint [15] 0 0
24 hours post-dose at Week 30
Primary outcome [16] 0 0
AUC0-24h of Total OCA at Week 30
Timepoint [16] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [17] 0 0
Cmax of Total OCA at Week 48
Timepoint [17] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [18] 0 0
Tmax of Total OCA at Week 48
Timepoint [18] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [19] 0 0
Ctrough of Total OCA at Week 48
Timepoint [19] 0 0
24 hours post-dose at Week 48
Primary outcome [20] 0 0
AUC0-24h of Total OCA at Week 48
Timepoint [20] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [21] 0 0
Cmax of Unconjugated OCA at Week 12
Timepoint [21] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [22] 0 0
Tmax of Unconjugated OCA at Week 12
Timepoint [22] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [23] 0 0
Ctrough of Unconjugated OCA at Week 12
Timepoint [23] 0 0
24 hours post-dose at Week 12
Primary outcome [24] 0 0
AUC0-24h of Unconjugated OCA at Week 12
Timepoint [24] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [25] 0 0
Cmax of Unconjugated OCA at Week 18
Timepoint [25] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [26] 0 0
Tmax of Unconjugated OCA at Week 18
Timepoint [26] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [27] 0 0
Ctrough of Unconjugated OCA at Week 18
Timepoint [27] 0 0
24 hours post-dose at Week 18
Primary outcome [28] 0 0
AUC0-24h of Unconjugated OCA at Week 18
Timepoint [28] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [29] 0 0
Cmax of Unconjugated OCA at Week 24
Timepoint [29] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [30] 0 0
Tmax of Unconjugated OCA at Week 24
Timepoint [30] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [31] 0 0
Ctrough of Unconjugated OCA at Week 24
Timepoint [31] 0 0
24 hours post-dose at Week 24
Primary outcome [32] 0 0
AUC0-24h of Unconjugated OCA at Week 24
Timepoint [32] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [33] 0 0
Cmax of Unconjugated OCA at Week 30
Timepoint [33] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [34] 0 0
Tmax of Unconjugated OCA at Week 30
Timepoint [34] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [35] 0 0
Ctrough of Unconjugated OCA at Week 30
Timepoint [35] 0 0
24 hours post-dose at Week 30
Primary outcome [36] 0 0
AUC0-24h of Unconjugated OCA at Week 30
Timepoint [36] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [37] 0 0
Cmax of Unconjugated OCA at Week 48
Timepoint [37] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [38] 0 0
Tmax of Unconjugated OCA at Week 48
Timepoint [38] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [39] 0 0
Ctrough of Unconjugated OCA at Week 48
Timepoint [39] 0 0
24 hours post-dose at Week 48
Primary outcome [40] 0 0
AUC0-24h of Unconjugated OCA at Week 48
Timepoint [40] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [41] 0 0
Cmax of Glyco Conjugate of OCA (Glyco-OCA) at Week 12
Timepoint [41] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [42] 0 0
Tmax of Glyco-OCA at Week 12
Timepoint [42] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [43] 0 0
Ctrough of Glyco-OCA at Week 12
Timepoint [43] 0 0
24 hours post-dose at Week 12
Primary outcome [44] 0 0
AUC0-24h of Glyco-OCA at Week 12
Timepoint [44] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [45] 0 0
Metabolite to Parent Ratio of AUC-0-24h (MRAUC) of Glyco-OCA at Week 12
Timepoint [45] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [46] 0 0
Metabolite to Parent Ratio of Cmax (MRCmax) of Glyco-OCA at Week 12
Timepoint [46] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [47] 0 0
Cmax of Glyco-OCA at Week 18
Timepoint [47] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [48] 0 0
Tmax of Glyco-OCA at Week 18
Timepoint [48] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [49] 0 0
Ctrough of Glyco-OCA at Week 18
Timepoint [49] 0 0
24 hours post-dose at Week 18
Primary outcome [50] 0 0
AUC0-24h of Glyco-OCA at Week 18
Timepoint [50] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [51] 0 0
MRAUC of Glyco-OCA at Week 18
Timepoint [51] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [52] 0 0
MRCmax of Glyco-OCA at Week 18
Timepoint [52] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [53] 0 0
Cmax of Glyco-OCA at Week 24
Timepoint [53] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [54] 0 0
Tmax of Glyco-OCA at Week 24
Timepoint [54] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [55] 0 0
Ctrough of Glyco-OCA at Week 24
Timepoint [55] 0 0
24 hours post-dose at Week 24
Primary outcome [56] 0 0
AUC0-24h of Glyco-OCA at Week 24
Timepoint [56] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [57] 0 0
MRAUC of Glyco-OCA at Week 24
Timepoint [57] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [58] 0 0
MRCmax of Glyco-OCA at Week 24
Timepoint [58] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [59] 0 0
Cmax of Glyco-OCA at Week 30
Timepoint [59] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [60] 0 0
Tmax of Glyco-OCA at Week 30
Timepoint [60] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [61] 0 0
Ctrough of Glyco-OCA at Week 30
Timepoint [61] 0 0
24 hours post-dose at Week 30
Primary outcome [62] 0 0
AUC0-24h of Glyco-OCA at Week 30
Timepoint [62] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [63] 0 0
MRAUC of Glyco-OCA at Week 30
Timepoint [63] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [64] 0 0
MRCmax of Glyco-OCA at Week 30
Timepoint [64] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [65] 0 0
Cmax of Glyco-OCA at Week 48
Timepoint [65] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [66] 0 0
Tmax of Glyco-OCA at Week 48
Timepoint [66] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [67] 0 0
Ctrough of Glyco-OCA at Week 48
Timepoint [67] 0 0
24 hours post-dose at Week 48
Primary outcome [68] 0 0
AUC0-24h of Glyco-OCA at Week 48
Timepoint [68] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [69] 0 0
MRAUC of Glyco-OCA at Week 48
Timepoint [69] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [70] 0 0
MRCmax of Glyco-OCA at Week 48
Timepoint [70] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [71] 0 0
Cmax of Tauro Conjugate of OCA (Tauro-OCA) at Week 12
Timepoint [71] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [72] 0 0
Tmax of Tauro-OCA at Week 12
Timepoint [72] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [73] 0 0
Ctrough of Tauro-OCA at Week 12
Timepoint [73] 0 0
24 hours post-dose at Week 12
Primary outcome [74] 0 0
AUC0-24h of Tauro-OCA at Week 12
Timepoint [74] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [75] 0 0
MRAUC of Tauro-OCA at Week 12
Timepoint [75] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [76] 0 0
MRCmax of Tauro-OCA at Week 12
Timepoint [76] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [77] 0 0
Cmax of Tauro-OCA at Week 18
Timepoint [77] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [78] 0 0
Tmax of Tauro-OCA at Week 18
Timepoint [78] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [79] 0 0
Ctrough of Tauro-OCA at Week 18
Timepoint [79] 0 0
24 hours post-dose at Week 18
Primary outcome [80] 0 0
AUC0-24h of Tauro-OCA at Week 18
Timepoint [80] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [81] 0 0
MRAUC of Tauro-OCA at Week 18
Timepoint [81] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [82] 0 0
MRCmax of Tauro-OCA at Week 18
Timepoint [82] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [83] 0 0
Cmax of Tauro-OCA at Week 24
Timepoint [83] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [84] 0 0
Tmax of Tauro-OCA at Week 24
Timepoint [84] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [85] 0 0
Ctrough of Tauro-OCA at Week 24
Timepoint [85] 0 0
24 hours post-dose at Week 24
Primary outcome [86] 0 0
AUC0-24h of Tauro-OCA at Week 24
Timepoint [86] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [87] 0 0
MRAUC of Tauro-OCA at Week 24
Timepoint [87] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [88] 0 0
MRCmax of Tauro-OCA at Week 24
Timepoint [88] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [89] 0 0
Cmax of Tauro-OCA at Week 30
Timepoint [89] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [90] 0 0
Tmax of Tauro-OCA at Week 30
Timepoint [90] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [91] 0 0
Ctrough of Tauro-OCA at Week 30
Timepoint [91] 0 0
24 hours post-dose at Week 30
Primary outcome [92] 0 0
AUC0-24h of Tauro-OCA at Week 30
Timepoint [92] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [93] 0 0
MRAUC of Tauro-OCA at Week 30
Timepoint [93] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [94] 0 0
MRCmax of Tauro-OCA at Week 30
Timepoint [94] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [95] 0 0
Cmax of Tauro-OCA at Week 48
Timepoint [95] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [96] 0 0
Tmax of Tauro-OCA at Week 48
Timepoint [96] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [97] 0 0
Ctrough of Tauro-OCA at Week 48
Timepoint [97] 0 0
24 hours post-dose at Week 48
Primary outcome [98] 0 0
AUC0-24h of Tauro-OCA at Week 48
Timepoint [98] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [99] 0 0
MRAUC of Tauro-OCA at Week 48
Timepoint [99] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [100] 0 0
MRCmax of Tauro-OCA at Week 48
Timepoint [100] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [101] 0 0
Cmax of Glucuronide Metabolite of OCA (OCA-glucuronide) at Week 12
Timepoint [101] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [102] 0 0
Tmax of OCA-glucuronide at Week 12
Timepoint [102] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [103] 0 0
Ctrough of OCA-glucuronide at Week 12
Timepoint [103] 0 0
24 hours post-dose at Week 12
Primary outcome [104] 0 0
AUC0-24h of OCA-glucuronide at Week 12
Timepoint [104] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [105] 0 0
MRAUC of OCA-glucuronide at Week 12
Timepoint [105] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [106] 0 0
MRCmax of OCA-glucuronide at Week 12
Timepoint [106] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary outcome [107] 0 0
Cmax of OCA-glucuronide at Week 18
Timepoint [107] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [108] 0 0
Tmax of OCA-glucuronide at Week 18
Timepoint [108] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [109] 0 0
Ctrough of OCA-glucuronide at Week 18
Timepoint [109] 0 0
24 hours post-dose at Week 18
Primary outcome [110] 0 0
AUC0-24h of OCA-glucuronide at Week 18
Timepoint [110] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [111] 0 0
MRAUC of OCA-glucuronide at Week 18
Timepoint [111] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [112] 0 0
MRCmax of OCA-glucuronide at Week 18
Timepoint [112] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary outcome [113] 0 0
Cmax of OCA-glucuronide at Week 24
Timepoint [113] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [114] 0 0
Tmax of OCA-glucuronide at Week 24
Timepoint [114] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [115] 0 0
Ctrough of OCA-glucuronide at Week 24
Timepoint [115] 0 0
24 hours post-dose at Week 24
Primary outcome [116] 0 0
AUC0-24h of OCA-glucuronide at Week 24
Timepoint [116] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [117] 0 0
MRAUC of OCA-glucuronide at Week 24
Timepoint [117] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [118] 0 0
MRCmax of OCA-glucuronide at Week 24
Timepoint [118] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary outcome [119] 0 0
Cmax of OCA-glucuronide at Week 30
Timepoint [119] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [120] 0 0
Tmax of OCA-glucuronide at Week 30
Timepoint [120] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [121] 0 0
Ctrough of OCA-glucuronide at Week 30
Timepoint [121] 0 0
24 hours post-dose at Week 30
Primary outcome [122] 0 0
AUC0-24h of OCA-glucuronide at Week 30
Timepoint [122] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [123] 0 0
MRAUC of OCA-glucuronide at Week 30
Timepoint [123] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [124] 0 0
MRCmax of OCA-glucuronide at Week 30
Timepoint [124] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary outcome [125] 0 0
Cmax of OCA-glucuronide at Week 48
Timepoint [125] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [126] 0 0
Tmax of OCA-glucuronide at Week 48
Timepoint [126] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [127] 0 0
Ctrough of OCA-glucuronide at Week 48
Timepoint [127] 0 0
24 hours post-dose at Week 48
Primary outcome [128] 0 0
AUC0-24h of OCA-glucuronide at Week 48
Timepoint [128] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [129] 0 0
MRAUC of OCA-glucuronide at Week 48
Timepoint [129] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [130] 0 0
MRCmax of OCA-glucuronide at Week 48
Timepoint [130] 0 0
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary outcome [131] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [131] 0 0
Baseline up to approximately 3 years
Secondary outcome [1] 0 0
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [1] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [2] 0 0
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [2] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [3] 0 0
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [3] 0 0
Baseline, Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [4] 0 0
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Timepoint [4] 0 0
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [5] 0 0
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Timepoint [5] 0 0
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [6] 0 0
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Timepoint [6] 0 0
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [7] 0 0
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Timepoint [7] 0 0
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [8] 0 0
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Timepoint [8] 0 0
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [9] 0 0
Change From Baseline in Total Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [9] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [10] 0 0
Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [10] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [11] 0 0
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [11] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [12] 0 0
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [12] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [13] 0 0
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [13] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [14] 0 0
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [14] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [15] 0 0
Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [15] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [16] 0 0
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [16] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [17] 0 0
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [17] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [18] 0 0
Change From Baseline in Platelets at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Timepoint [18] 0 0
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary outcome [19] 0 0
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Timepoint [19] 0 0
Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Secondary outcome [20] 0 0
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Timepoint [20] 0 0
Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Secondary outcome [21] 0 0
Change From Baseline in 7a-hydroxy-4-cholesten-3-one (C4) at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Timepoint [21] 0 0
Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Secondary outcome [22] 0 0
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Timepoint [22] 0 0
Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

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

* History of elevated alkaline phosphatase (ALP) levels for at least 6 months
* Positive antimitochondrial antibody (AMA) titer or if AMA negative or low titer (=1:80), PBC specific antibodies (anti-glycoprotein 210 [GP210] and/or anti-SP100) and/or antibodies against the major M2 components (E2 component of mitochondrial pyruvate dehydrogenase complex [PDC-E2], 2-oxo-glutaric acid dehydrogenase complex)
* Liver biopsy consistent with PBC (collected at any time prior to Screening)
2. Evidence of cirrhosis including at least one of the following:

* Biopsy results consistent with PBC Stage 4
* Liver stiffness as assessed by Transient Elastography (TE) Median Value =16.9 kilopascals (kPa)
* Clinical evidence in the absence of acute liver failure consistent with cirrhosis including: gastroesophageal varices, ascites, radiological evidence of cirrhosis (nodular liver or enlargement of portal vein and splenomegaly)
* Combined low platelet count (<140,000/cubic millimeter [mm^3]) with

* persistent decrease in serum albumin, or
* elevation in prothrombin time/international normalized ratio (INR) (not due to antithrombotic agent use), or
* elevated bilirubin (2*upper limit of normal [ULN])
3. Satisfy the criteria of the modified Child-Pugh (CP) classification for hepatic impairment during Screening:

* Moderate: CP-B (Scores 7 to 9) or
* Severe: CP-C (Scores 10 to 12)
4. Model of end-stage liver disease (MELD) score of 6 to 24 at Screening
5. Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for =3 months) prior to Day 1, or unable to tolerate or unresponsive to UDCA (no UDCA for =3 months)
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Non-cirrhotic or cirrhotic CP-A (Mild; Score 5 to 6)
2. History of liver transplant or organ transplant
3. History of alcohol or drug abuse within 12 months prior to Screening
4. Hepatic encephalopathy (as defined by a West Haven score of =2
5. History or presence of other concomitant liver diseases including:

* Hepatitis C virus infection and ribonucleic acid (RNA) positive
* Active hepatitis B infection; however, participants who have seroconverted (hepatitis B surface antigen and hepatitis B e antigen negative) may be included in this study after consultation with the medical monitor
* Primary sclerosing cholangitis
* Alcoholic liver disease
* Definite autoimmune liver disease or overlap hepatitis
* Gilbert's Syndrome
6. In the opinion of the Investigator, fluctuating or rapidly deteriorating hepatic function prior to randomization

Other inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/07/2021
Sample size
Target
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Nepean Hospital - Kingswood
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Caba
Country [11] 0 0
Argentina
State/province [11] 0 0
Ciudad Autonoma de Buenos Aire
Country [12] 0 0
Argentina
State/province [12] 0 0
Mendoza
Country [13] 0 0
Argentina
State/province [13] 0 0
Pilar
Country [14] 0 0
Argentina
State/province [14] 0 0
Rosario
Country [15] 0 0
Belgium
State/province [15] 0 0
Brussels
Country [16] 0 0
Belgium
State/province [16] 0 0
Edegem
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Brazil
State/province [18] 0 0
Belo Horizonte
Country [19] 0 0
Brazil
State/province [19] 0 0
Rio Grande
Country [20] 0 0
Brazil
State/province [20] 0 0
São Paulo
Country [21] 0 0
Canada
State/province [21] 0 0
Toronto
Country [22] 0 0
Estonia
State/province [22] 0 0
Tallinn
Country [23] 0 0
Estonia
State/province [23] 0 0
Tartu
Country [24] 0 0
Germany
State/province [24] 0 0
Leipzig
Country [25] 0 0
Hungary
State/province [25] 0 0
Bekescsaba
Country [26] 0 0
Italy
State/province [26] 0 0
MB
Country [27] 0 0
Italy
State/province [27] 0 0
Modena
Country [28] 0 0
Lithuania
State/province [28] 0 0
Kaunas
Country [29] 0 0
Lithuania
State/province [29] 0 0
Klaipeda
Country [30] 0 0
Lithuania
State/province [30] 0 0
Vilnius
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Sevilla
Country [33] 0 0
Spain
State/province [33] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Intercept Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 4, randomized, double-blind, placebo-controlled study will evaluate the pharmacokinetics (PK) and safety of OCA treatment in participants with PBC and moderate to severe hepatic impairment over a 48-week treatment period. Participants who have completed their 48-week double blind treatment period will continue double-blind treatment until all randomized participants have completed their 48-week treatment period and the database for that period is locked. An open-label extension study in which all participants receive OCA will be considered following review of blinded safety and PK data.
Trial website
https://clinicaltrials.gov/study/NCT03633227
Trial related presentations / publications
Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. No abstract available.
Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60(2):715-35. doi: 10.1002/hep.27210. Epub 2014 Jul 8. No abstract available.
Public notes

Contacts
Principal investigator
Name 0 0
Steven Shiff, M.D.
Address 0 0
Intercept Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03633227