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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02308111




Registration number
NCT02308111
Ethics application status
Date submitted
10/11/2014
Date registered
4/12/2014
Date last updated
9/03/2023

Titles & IDs
Public title
Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cholangitis
Scientific title
A Phase 4, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Effect of Obeticholic Acid on Clinical Outcomes in Patients With Primary Biliary Cholangitis
Secondary ID [1] 0 0
747-302
Universal Trial Number (UTN)
Trial acronym
COBALT
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) 5 mg to 10 mg - Obeticholic Acid (OCA) 5 mg for a minimum 3 months and then titrating up to a maximum 10 mg for the remainder of the trial (based on tolerability and CP Score).

Placebo comparator: Placebo -


Treatment: Drugs: Obeticholic Acid (OCA)
Non-cirrhotic and classified as CP Class A: 5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily based on tolerability at 3 months for the duration of the study (majority of participants).

Cirrhotic and classified as CP Class B and C: 5 mg tablet of OCA once weekly for at least 3 months, subsequently titrating up to a maximum dose and frequency of 10 mg OCA twice weekly based on tolerability and biochemical response for the duration of the study.

Treatment: Drugs: Placebo
One tablet daily (or a lower frequency depending on CP score) for the remainder of the study

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to the First Occurrence of Composite Endpoint
Timepoint [1] 0 0
Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years)
Primary outcome [2] 0 0
Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint)
Timepoint [2] 0 0
Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years)
Secondary outcome [1] 0 0
Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint
Timepoint [1] 0 0
Time to first occurrence from date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to 7 years)
Secondary outcome [2] 0 0
Time To Liver Transplant Or Death (All-cause)
Timepoint [2] 0 0
Time to first occurrence from date of randomization until the date of first documented liver transplant or date of death from any cause (up to 7 years)
Secondary outcome [3] 0 0
Time to First Occurrence of Fatal Event (All-Cause)
Timepoint [3] 0 0
Time to first occurrence from date of randomization until the date of death from any cause (up to 7 years)
Secondary outcome [4] 0 0
Time to First Occurrence of Liver Transplant
Timepoint [4] 0 0
Time to first occurrence from date of randomization until the date of first documented liver transplant or date of death from any cause (up to 5 years)
Secondary outcome [5] 0 0
Time to First Occurrence of Hospitalization Due to Hepatic Events
Timepoint [5] 0 0
Time to first occurrence from date of randomization until the date of hospitalization, liver transplant or death from any cause, whichever came first (up to 5 years)
Secondary outcome [6] 0 0
Time to First Occurrence of Uncontrolled or Refractory Ascites
Timepoint [6] 0 0
Time to first occurrence from date of randomization until the date of first documented uncontrolled or refractory ascites, liver transplant or date of death from any cause, whichever came first (up to 5 years)
Secondary outcome [7] 0 0
Time to First Occurrence of MELD Score =15
Timepoint [7] 0 0
Time to first occurrence from date of randomization until the date of first documented MELD Score =15, liver transplant or date of death from any cause, whichever came first (up to 5 years)
Secondary outcome [8] 0 0
Time To Development Of Varix/Varices
Timepoint [8] 0 0
Time to first occurrence from date of randomization until the date of first documented development of varix/varices, liver transplant or death from any cause, whichever came first (up to 5 years)
Secondary outcome [9] 0 0
Time To Liver-Related Death
Timepoint [9] 0 0
Time to first occurrence from date of randomization until the date of first liver-related or non-liver- related death, whichever came first (up to 5 years)
Secondary outcome [10] 0 0
Time To Liver-Related Death Or Liver Transplant
Timepoint [10] 0 0
Time to first occurrence from date of randomization until the date of liver transplant, liver-related death or non-liver-related death from any cause, whichever came first (up to 5 years)
Secondary outcome [11] 0 0
Time To Liver-Related Death, Liver Transplant, Or MELD Score =15
Timepoint [11] 0 0
Time to first occurrence from date of randomization until the date of liver transplant, liver-related death, non-liver-related death from any cause or MELD Score =15, whichever came first (up to 5 years)
Secondary outcome [12] 0 0
Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline)
Timepoint [12] 0 0
Time to first occurrence from date of randomization until the date of cirrhosis, liver transplant or death from any cause, whichever came first (up to 5 years)
Secondary outcome [13] 0 0
Time To Occurrence Of Hepatocellular Carcinoma (HCC)
Timepoint [13] 0 0
Time to first occurrence from date of randomization until the date of HCC diagnosis, liver transplant or death from any cause, whichever came first (up to 5 years)
Secondary outcome [14] 0 0
Change From Baseline To Month 24 Of Total Bilirubin
Timepoint [14] 0 0
Baseline up to Month 24
Secondary outcome [15] 0 0
Change From Baseline To Month 24 Of Direct Bilirubin
Timepoint [15] 0 0
Baseline up to Month 24
Secondary outcome [16] 0 0
Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST)
Timepoint [16] 0 0
Baseline up to Month 24
Secondary outcome [17] 0 0
Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT)
Timepoint [17] 0 0
Baseline up to Month 24
Secondary outcome [18] 0 0
Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP)
Timepoint [18] 0 0
Baseline up to Month 24
Secondary outcome [19] 0 0
Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT)
Timepoint [19] 0 0
Baseline up to Month 24
Secondary outcome [20] 0 0
Change From Baseline To Month 24 Of Albumin
Timepoint [20] 0 0
Baseline up to Month 24
Secondary outcome [21] 0 0
Change From Baseline To Month 24 Of INR
Timepoint [21] 0 0
Baseline up to Month 24
Secondary outcome [22] 0 0
Change From Baseline To Month 72 Of MELD Score
Timepoint [22] 0 0
Baseline up to Month 72
Secondary outcome [23] 0 0
Change From Baseline To Month 72 Of MELD-Na Score
Timepoint [23] 0 0
Baseline up to Month 72
Secondary outcome [24] 0 0
Change From Baseline To Month 72 Of CPS
Timepoint [24] 0 0
Baseline up to Month 72
Secondary outcome [25] 0 0
Change From Baseline To Month 72 Of Mayo Risk Score (MRS)
Timepoint [25] 0 0
Baseline up to Month 72
Secondary outcome [26] 0 0
Change From Baseline To Month 72 Of Immunoglobulin-M (IgM)
Timepoint [26] 0 0
Baseline up to Month 72
Secondary outcome [27] 0 0
Change From Baseline To Month 72 Of C-reactive Protein (CRP)
Timepoint [27] 0 0
Baseline up to Month 72
Secondary outcome [28] 0 0
Change From Baseline To Month 72 Of Tumor Necrosis Factor-a (TNF-a)
Timepoint [28] 0 0
Baseline up to Month 72
Secondary outcome [29] 0 0
Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19)
Timepoint [29] 0 0
Baseline up to Month 72
Secondary outcome [30] 0 0
Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18)
Timepoint [30] 0 0
Baseline up to Month 72
Secondary outcome [31] 0 0
Change From Baseline To Month 72 Of 7a-hydroxy-4-cholesten-3-one (C4)
Timepoint [31] 0 0
Baseline up to Month 72
Secondary outcome [32] 0 0
Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF)
Timepoint [32] 0 0
Baseline up to Month 72
Secondary outcome [33] 0 0
Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography
Timepoint [33] 0 0
Baseline up to Month 72
Secondary outcome [34] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [34] 0 0
Baseline up to the last IP dose plus 30 days and prior to commercial OCA initiation date (up to 7 years)
Secondary outcome [35] 0 0
Pharmacokinetic (PK) Population: Fasting Trough Concentrations Of OCA By Dose Regimen
Timepoint [35] 0 0
Months 3, 6, 9, 12, 24, 36, 48, and 60
Secondary outcome [36] 0 0
PK Population: Serial Concentration of OCA By Dose Regimen
Timepoint [36] 0 0
Month 9
Secondary outcome [37] 0 0
PK Population: Area Under The Concentration-Time Curve (AUC) From 0 to 6 Hours Post-dose (AUC0-6h) Of Participants Who Received 5 mg QD OCA and With CP Score=Non-Cirrhotic (NC)
Timepoint [37] 0 0
Month 9
Secondary outcome [38] 0 0
PK Population: AUC From 0 to 24 Hours Post-dose (AUC0-24h) Of Participants Who Received 5 mg QD OCA and With CP Score=NC
Timepoint [38] 0 0
Month 9
Secondary outcome [39] 0 0
PK Population: Maximum Observed Concentration (Cmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC
Timepoint [39] 0 0
Month 9
Secondary outcome [40] 0 0
PK Population: Time to Cmax (Tmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC
Timepoint [40] 0 0
Month 9
Secondary outcome [41] 0 0
PK Population: Metabolite to Parent Ratio of AUC0-6h (MRAUC) Of Participants Who Received 5mg QD OCA and With CP Score=NC
Timepoint [41] 0 0
Month 9
Secondary outcome [42] 0 0
PK Population: Metabolite to Parent Ratio of Cmax (MRCmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC
Timepoint [42] 0 0
Month 9
Secondary outcome [43] 0 0
PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With CP Score=A
Timepoint [43] 0 0
Month 9
Secondary outcome [44] 0 0
PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With CP Score=A
Timepoint [44] 0 0
Month 9
Secondary outcome [45] 0 0
PK Population: Cmax Of Participants Who Received 5mg QD OCA and With CP Score=A
Timepoint [45] 0 0
Month 9
Secondary outcome [46] 0 0
PK Population: Tmax Of Participants Who Received 5mg QD OCA and With CP Score=A
Timepoint [46] 0 0
Month 9
Secondary outcome [47] 0 0
PK Population: Concentration at 24 Hours Post-dose (Ctrough) Of Participants Who Received 5mg QD OCA and With CP Score=A
Timepoint [47] 0 0
Month 9
Secondary outcome [48] 0 0
PK Population: MRAUC Of Participants Who Received 5mg QD OCA and With CP Score=A
Timepoint [48] 0 0
Month 9
Secondary outcome [49] 0 0
PK Population: MRCmax Of Participants Who Received 5mg QD OCA and With CP Score=A
Timepoint [49] 0 0
Month 9
Secondary outcome [50] 0 0
PK Population: Ctrough Of Participants Who Received 5mg QD OCA and With CP Score=B
Timepoint [50] 0 0
Month 9
Secondary outcome [51] 0 0
PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC
Timepoint [51] 0 0
Month 9
Secondary outcome [52] 0 0
PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC
Timepoint [52] 0 0
Month 9
Secondary outcome [53] 0 0
PK Population: Cmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC
Timepoint [53] 0 0
Month 9
Secondary outcome [54] 0 0
PK Population: Tmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC
Timepoint [54] 0 0
Month 9
Secondary outcome [55] 0 0
PK Population: Ctrough Of Participants Who Received 5mg QOD OCA and With CP Score=NC
Timepoint [55] 0 0
Month 9
Secondary outcome [56] 0 0
PK Population: MRAUC Of Participants Who Received 5mg QOD OCA and With CP Score=NC
Timepoint [56] 0 0
Month 9
Secondary outcome [57] 0 0
PK Population: MRCmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC
Timepoint [57] 0 0
Month 9
Secondary outcome [58] 0 0
PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=NC
Timepoint [58] 0 0
Month 9
Secondary outcome [59] 0 0
PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CP Score=NC
Timepoint [59] 0 0
Month 9
Secondary outcome [60] 0 0
PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC
Timepoint [60] 0 0
Month 9
Secondary outcome [61] 0 0
PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC
Timepoint [61] 0 0
Month 9
Secondary outcome [62] 0 0
PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=NC
Timepoint [62] 0 0
Month 9
Secondary outcome [63] 0 0
PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=NC
Timepoint [63] 0 0
Month 9
Secondary outcome [64] 0 0
PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC
Timepoint [64] 0 0
Month 9
Secondary outcome [65] 0 0
PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=A
Timepoint [65] 0 0
Month 9
Secondary outcome [66] 0 0
PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CPS Score=A
Timepoint [66] 0 0
Month 9
Secondary outcome [67] 0 0
PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=A
Timepoint [67] 0 0
Month 9
Secondary outcome [68] 0 0
PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CPS Score=A
Timepoint [68] 0 0
Month 9
Secondary outcome [69] 0 0
PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=A
Timepoint [69] 0 0
Month 9
Secondary outcome [70] 0 0
PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=A
Timepoint [70] 0 0
Month 9
Secondary outcome [71] 0 0
PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=A
Timepoint [71] 0 0
Month 9
Secondary outcome [72] 0 0
PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
Timepoint [72] 0 0
Month 9
Secondary outcome [73] 0 0
PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
Timepoint [73] 0 0
Month 9
Secondary outcome [74] 0 0
PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
Timepoint [74] 0 0
Month 9
Secondary outcome [75] 0 0
PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
Timepoint [75] 0 0
Month 9
Secondary outcome [76] 0 0
PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
Timepoint [76] 0 0
Month 9
Secondary outcome [77] 0 0
PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
Timepoint [77] 0 0
Month 9
Secondary outcome [78] 0 0
PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
Timepoint [78] 0 0
Month 9
Secondary outcome [79] 0 0
PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=A
Timepoint [79] 0 0
Month 9
Secondary outcome [80] 0 0
PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=A
Timepoint [80] 0 0
Month 9
Secondary outcome [81] 0 0
PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A
Timepoint [81] 0 0
Month 9
Secondary outcome [82] 0 0
PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A
Timepoint [82] 0 0
Month 9
Secondary outcome [83] 0 0
PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=A
Timepoint [83] 0 0
Month 9
Secondary outcome [84] 0 0
PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=A
Timepoint [84] 0 0
Month 9
Secondary outcome [85] 0 0
PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A
Timepoint [85] 0 0
Month 9
Secondary outcome [86] 0 0
PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=B
Timepoint [86] 0 0
Month 9
Secondary outcome [87] 0 0
PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=B
Timepoint [87] 0 0
Month 9
Secondary outcome [88] 0 0
PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B
Timepoint [88] 0 0
Month 9
Secondary outcome [89] 0 0
PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B
Timepoint [89] 0 0
Month 9
Secondary outcome [90] 0 0
PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=B
Timepoint [90] 0 0
Month 9
Secondary outcome [91] 0 0
PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=B
Timepoint [91] 0 0
Month 9
Secondary outcome [92] 0 0
PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B
Timepoint [92] 0 0
Month 9
Secondary outcome [93] 0 0
PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
Timepoint [93] 0 0
Month 9
Secondary outcome [94] 0 0
PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
Timepoint [94] 0 0
Month 9
Secondary outcome [95] 0 0
PK Population: Cmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
Timepoint [95] 0 0
Month 9
Secondary outcome [96] 0 0
PK Population: Tmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
Timepoint [96] 0 0
Month 9
Secondary outcome [97] 0 0
PK Population: Ctrough Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
Timepoint [97] 0 0
Month 9
Secondary outcome [98] 0 0
PK Population: MRAUC Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
Timepoint [98] 0 0
Month 9
Secondary outcome [99] 0 0
PK Population: MRCmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
Timepoint [99] 0 0
Month 9
Secondary outcome [100] 0 0
PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=A
Timepoint [100] 0 0
Month 9
Secondary outcome [101] 0 0
PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=A
Timepoint [101] 0 0
Month 9
Secondary outcome [102] 0 0
PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A
Timepoint [102] 0 0
Month 9
Secondary outcome [103] 0 0
PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A
Timepoint [103] 0 0
Month 9
Secondary outcome [104] 0 0
PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=A
Timepoint [104] 0 0
Month 9
Secondary outcome [105] 0 0
PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=A
Timepoint [105] 0 0
Month 9
Secondary outcome [106] 0 0
PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A
Timepoint [106] 0 0
Month 9
Secondary outcome [107] 0 0
PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=B
Timepoint [107] 0 0
Month 9
Secondary outcome [108] 0 0
PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=B
Timepoint [108] 0 0
Month 9
Secondary outcome [109] 0 0
PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B
Timepoint [109] 0 0
Month 9
Secondary outcome [110] 0 0
PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B
Timepoint [110] 0 0
Month 9
Secondary outcome [111] 0 0
PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=B
Timepoint [111] 0 0
Month 9
Secondary outcome [112] 0 0
PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=B
Timepoint [112] 0 0
Month 9
Secondary outcome [113] 0 0
PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B
Timepoint [113] 0 0
Month 9
Secondary outcome [114] 0 0
PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
Timepoint [114] 0 0
Month 9
Secondary outcome [115] 0 0
PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
Timepoint [115] 0 0
Month 9
Secondary outcome [116] 0 0
PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
Timepoint [116] 0 0
Month 9
Secondary outcome [117] 0 0
PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
Timepoint [117] 0 0
Month 9
Secondary outcome [118] 0 0
PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
Timepoint [118] 0 0
Month 9
Secondary outcome [119] 0 0
PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
Timepoint [119] 0 0
Month 9
Secondary outcome [120] 0 0
PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
Timepoint [120] 0 0
Month 9
Secondary outcome [121] 0 0
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QD OCA
Timepoint [121] 0 0
Months 3, 6, 12, 24, and 48
Secondary outcome [122] 0 0
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QD OCA
Timepoint [122] 0 0
Months 3, 6, 9, 12, and 24
Secondary outcome [123] 0 0
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QOD OCA
Timepoint [123] 0 0
Months 6, 12, and 24
Secondary outcome [124] 0 0
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QOD OCA
Timepoint [124] 0 0
Months 3, 6, and 12
Secondary outcome [125] 0 0
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QW OCA
Timepoint [125] 0 0
Months 6 and 12
Secondary outcome [126] 0 0
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QW OCA
Timepoint [126] 0 0
Month 12
Secondary outcome [127] 0 0
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg Q2W OCA
Timepoint [127] 0 0
Months 6, 24, 36 and 48
Secondary outcome [128] 0 0
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg Q2W OCA
Timepoint [128] 0 0
Months 3, 6, 12, 24, 36, and 48
Secondary outcome [129] 0 0
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QD OCA
Timepoint [129] 0 0
Months 6, 9, 12, 24, 36, and 60
Secondary outcome [130] 0 0
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QD OCA
Timepoint [130] 0 0
Months 6, 9, 12, 24, and 36
Secondary outcome [131] 0 0
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QOD OCA
Timepoint [131] 0 0
Months 3, 6, 9, 12, 24, 36, 48, and 60
Secondary outcome [132] 0 0
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QOD OCA
Timepoint [132] 0 0
Month 12
Secondary outcome [133] 0 0
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg Q2W OCA
Timepoint [133] 0 0
Month 6
Secondary outcome [134] 0 0
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg Q2W OCA
Timepoint [134] 0 0
Month 6

Eligibility
Key inclusion criteria
Key

1. Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Diseases [AASLD] and the European Association for the Study of the Liver [EASL] practice guidelines; Lindor 2009; EASL 2009), as demonstrated by the presence of =2 of the following 3 diagnostic factors:

* History of elevated Alkaline phosphatase levels for at least 6 months
* Positive antimitochondrial antibody (AMA) titer or if AMA negative or in low titer (<1:80) PBC-specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
* Liver biopsy consistent with PBC
2. A mean total bilirubin >ULN and =5x ULN and/or a mean ALP >3x ULN
3. Either is not taking UDCA (no UDCA dose in the past 3 months) or has been taking UDCA for at least 12 months with a stable dose for =3 months prior to Day 0
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History or presence of other concomitant liver diseases including:

* Hepatitis C virus infection
* Active Hepatitis B infection; however, subjects 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 (PSC)
* Alcoholic liver disease
* Definite autoimmune liver disease or overlap hepatitis
* Nonalcoholic steatohepatitis (NASH)
* Gilbert's Syndrome
2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:

* History of liver transplant, current placement on a liver transplant list, or current Model of End Stage Liver Disease (MELD) score >12. Subjects who are placed on a transplant list despite a relatively early disease stage (for example per regional guidelines) may be eligible as long as they do not meet any of the other exclusion criteria
* Cirrhosis with complications, including history (within the past 12 months) or presence of:

* Variceal bleed
* Uncontrolled ascites
* Encephalopathy
* Spontaneous bacterial peritonitis
* Known or suspected HCC
* Prior transjugular intrahepatic portosystemic shunt procedure
* Hepatorenal syndrome (type I or II) or screening (Visit 1 or 2) serum creatinine >2 mg/dL (178 µmol/L)
3. Mean total bilirubin >5x ULN
4. Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures
5. Other medical conditions that may diminish life expectancy, including known cancers (except carcinomas in situ or other stable, relatively benign conditions)
6. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
7. Known history of human immunodeficiency virus infection
8. Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months)
9. Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study
10. History of alcohol abuse or other substance abuse within 1 year prior to Day 0
11. Participation in another investigational product, biologic, or medical device study within 30 days prior to Screening. Participation in a previous study of OCA is allowed with 3 months washout prior to enrollment in this study
12. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain
13. History of known or suspected clinically significant hypersensitivity to OCA or any of its components
14. UDCA naïve (unless contraindicated)

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Department of Gastroenterology & Hepatology, Nepean Hospital - Kingswood
Recruitment hospital [3] 0 0
Gallipoli Medical Research Foundation - Brisbane
Recruitment hospital [4] 0 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [6] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [7] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [8] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [9] 0 0
Fiona Stanley Hospital, Gastroenterology Department - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment postcode(s) [3] 0 0
4120 - Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
5042 - Adelaide
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
3065 - Fitzroy
Recruitment postcode(s) [8] 0 0
3084 - Heidelberg
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Mississippi
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
Argentina
State/province [24] 0 0
Buenos Aires
Country [25] 0 0
Argentina
State/province [25] 0 0
Cordoba
Country [26] 0 0
Argentina
State/province [26] 0 0
Santa Fe
Country [27] 0 0
Argentina
State/province [27] 0 0
Ciudad Autónoma de Buenos Aires
Country [28] 0 0
Austria
State/province [28] 0 0
Vienna
Country [29] 0 0
Belgium
State/province [29] 0 0
Antwerp
Country [30] 0 0
Belgium
State/province [30] 0 0
Vlaams-Brabant
Country [31] 0 0
Belgium
State/province [31] 0 0
Bruxelles
Country [32] 0 0
Belgium
State/province [32] 0 0
Ghent
Country [33] 0 0
Brazil
State/province [33] 0 0
Bahia
Country [34] 0 0
Brazil
State/province [34] 0 0
Campinas
Country [35] 0 0
Brazil
State/province [35] 0 0
Distrito Federal Brazil
Country [36] 0 0
Brazil
State/province [36] 0 0
Goias
Country [37] 0 0
Brazil
State/province [37] 0 0
Maranhao
Country [38] 0 0
Brazil
State/province [38] 0 0
Minas Gerais
Country [39] 0 0
Brazil
State/province [39] 0 0
Rio Grande Do Sul
Country [40] 0 0
Brazil
State/province [40] 0 0
Salvador
Country [41] 0 0
Brazil
State/province [41] 0 0
Sao Paulo
Country [42] 0 0
Brazil
State/province [42] 0 0
Rio de Janeiro
Country [43] 0 0
Bulgaria
State/province [43] 0 0
Sofia
Country [44] 0 0
Canada
State/province [44] 0 0
Alberta
Country [45] 0 0
Canada
State/province [45] 0 0
Manitoba
Country [46] 0 0
Canada
State/province [46] 0 0
Ontario
Country [47] 0 0
Canada
State/province [47] 0 0
Quebec
Country [48] 0 0
Chile
State/province [48] 0 0
V Región
Country [49] 0 0
Denmark
State/province [49] 0 0
Aarhus C
Country [50] 0 0
Denmark
State/province [50] 0 0
København Ø
Country [51] 0 0
Denmark
State/province [51] 0 0
Odense
Country [52] 0 0
Estonia
State/province [52] 0 0
Harju
Country [53] 0 0
Estonia
State/province [53] 0 0
Tartu
Country [54] 0 0
Finland
State/province [54] 0 0
Helsinki
Country [55] 0 0
Finland
State/province [55] 0 0
Turku,
Country [56] 0 0
France
State/province [56] 0 0
Paris
Country [57] 0 0
France
State/province [57] 0 0
Lille
Country [58] 0 0
France
State/province [58] 0 0
Pessac Cedex
Country [59] 0 0
Germany
State/province [59] 0 0
Hessen
Country [60] 0 0
Germany
State/province [60] 0 0
Lower Saxony
Country [61] 0 0
Germany
State/province [61] 0 0
QLD
Country [62] 0 0
Germany
State/province [62] 0 0
Berlin
Country [63] 0 0
Germany
State/province [63] 0 0
Hamburg
Country [64] 0 0
Germany
State/province [64] 0 0
Heidelberg
Country [65] 0 0
Germany
State/province [65] 0 0
Leipzig
Country [66] 0 0
Germany
State/province [66] 0 0
Munich
Country [67] 0 0
Hong Kong
State/province [67] 0 0
Pokfulam
Country [68] 0 0
Hong Kong
State/province [68] 0 0
Shatin
Country [69] 0 0
Hong Kong
State/province [69] 0 0
Tuen Mun, New Territories
Country [70] 0 0
Hong Kong
State/province [70] 0 0
Hong Kong
Country [71] 0 0
Hungary
State/province [71] 0 0
Bekescsaba
Country [72] 0 0
Hungary
State/province [72] 0 0
Budapest
Country [73] 0 0
Hungary
State/province [73] 0 0
Debrecen
Country [74] 0 0
Israel
State/province [74] 0 0
Nazareth Elit
Country [75] 0 0
Israel
State/province [75] 0 0
Beer Sheva
Country [76] 0 0
Israel
State/province [76] 0 0
Haifa
Country [77] 0 0
Israel
State/province [77] 0 0
Jerusalem
Country [78] 0 0
Israel
State/province [78] 0 0
Petach Tikva
Country [79] 0 0
Israel
State/province [79] 0 0
Ramat-Gan
Country [80] 0 0
Israel
State/province [80] 0 0
Tel-Aviv
Country [81] 0 0
Italy
State/province [81] 0 0
Cagliari
Country [82] 0 0
Italy
State/province [82] 0 0
Ancona
Country [83] 0 0
Italy
State/province [83] 0 0
Bologna
Country [84] 0 0
Italy
State/province [84] 0 0
Florence
Country [85] 0 0
Italy
State/province [85] 0 0
Milano
Country [86] 0 0
Italy
State/province [86] 0 0
Modena
Country [87] 0 0
Italy
State/province [87] 0 0
Monza
Country [88] 0 0
Italy
State/province [88] 0 0
Padova
Country [89] 0 0
Italy
State/province [89] 0 0
Palermo
Country [90] 0 0
Italy
State/province [90] 0 0
Rome
Country [91] 0 0
Korea, Republic of
State/province [91] 0 0
Busanjin-gu
Country [92] 0 0
Korea, Republic of
State/province [92] 0 0
Gangnam-gu
Country [93] 0 0
Korea, Republic of
State/province [93] 0 0
Gyeonggi-do
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Jongno-Gu
Country [95] 0 0
Korea, Republic of
State/province [95] 0 0
Seo-gu
Country [96] 0 0
Lithuania
State/province [96] 0 0
Kaunas
Country [97] 0 0
Lithuania
State/province [97] 0 0
Vilnius
Country [98] 0 0
Mexico
State/province [98] 0 0
Ciudad De Mexico,
Country [99] 0 0
Mexico
State/province [99] 0 0
DF
Country [100] 0 0
Netherlands
State/province [100] 0 0
Gelderland
Country [101] 0 0
Netherlands
State/province [101] 0 0
Noord-Holland
Country [102] 0 0
Netherlands
State/province [102] 0 0
Zuid Holland
Country [103] 0 0
Netherlands
State/province [103] 0 0
Amsterdam
Country [104] 0 0
Netherlands
State/province [104] 0 0
Utrecht
Country [105] 0 0
New Zealand
State/province [105] 0 0
Auckland
Country [106] 0 0
New Zealand
State/province [106] 0 0
Canterbury
Country [107] 0 0
Poland
State/province [107] 0 0
Kujawsko-Pomorskie
Country [108] 0 0
Poland
State/province [108] 0 0
Lover Silesia
Country [109] 0 0
Poland
State/province [109] 0 0
Masovia
Country [110] 0 0
Poland
State/province [110] 0 0
Mazovia
Country [111] 0 0
Poland
State/province [111] 0 0
Silesia
Country [112] 0 0
Poland
State/province [112] 0 0
Lublin
Country [113] 0 0
Portugal
State/province [113] 0 0
Lisbon
Country [114] 0 0
Serbia
State/province [114] 0 0
Belgrade
Country [115] 0 0
Spain
State/province [115] 0 0
Cantabria
Country [116] 0 0
Spain
State/province [116] 0 0
Madrid
Country [117] 0 0
Spain
State/province [117] 0 0
Barcelona
Country [118] 0 0
Spain
State/province [118] 0 0
Málaga
Country [119] 0 0
Spain
State/province [119] 0 0
Sevilla
Country [120] 0 0
Spain
State/province [120] 0 0
Valence
Country [121] 0 0
Sweden
State/province [121] 0 0
Huddinge
Country [122] 0 0
Sweden
State/province [122] 0 0
Gothenburg
Country [123] 0 0
Switzerland
State/province [123] 0 0
Bern
Country [124] 0 0
Switzerland
State/province [124] 0 0
St. Gallen
Country [125] 0 0
Switzerland
State/province [125] 0 0
Zurich
Country [126] 0 0
Turkey
State/province [126] 0 0
Ankara
Country [127] 0 0
Turkey
State/province [127] 0 0
Izmir
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Avon
Country [129] 0 0
United Kingdom
State/province [129] 0 0
Devon
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Lanarkshire
Country [131] 0 0
United Kingdom
State/province [131] 0 0
Scotland
Country [132] 0 0
United Kingdom
State/province [132] 0 0
Tyne And Wear
Country [133] 0 0
United Kingdom
State/province [133] 0 0
West Midlands
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Cambridge
Country [135] 0 0
United Kingdom
State/province [135] 0 0
London
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Nottingham

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Erik Ness, MD
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.