Download PDF

Clinical Trial Results:
A Phase 4, Double Blind, Randomized, Placebo Controlled, Multicenter Study Evaluating the Effect of Obeticholic Acid on Clinical Outcomes in Subjects with Primary Biliary Cholangitis. The COBALT Study Clinical Outcomes with Obeticholic Acid in Liver Treatment (COBALT)

Summary
EudraCT number	2014-005012-42
Trial protocol	HU LT AT BE DK FI GB EE ES NL FR DE BG PT
Global end of trial date	23 Dec 2021

Results information
Results version number	v1(current)
This version publication date	05 Jan 2023
First version publication date	05 Jan 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

747-302

ISRCTN number

US NCT number

NCT02308111

WHO universal trial number (UTN)

Sponsor organisation name

Intercept Pharmaceuticals, Inc.

Sponsor organisation address

305 Madison Avenue, Morristown, New Jersey, United States, 07960

Public contact

Steven Lauder, Intercept Pharmaceuticals, Inc., steven.lauder@interceptpharma.com

Scientific contact

Medical Information, Intercept Pharmaceuticals, Inc., medinfo@interceptpharma.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 Sep 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

23 Dec 2021

Global end of trial reached?

Yes

Global end of trial date

23 Dec 2021

Was the trial ended prematurely?

Yes

Main objective of the trial

The objective of this study is to assess the long-term efficacy of obeticholic acid (OCA) compared to placebo, in conjunction with the established local standard of care, on clinical outcomes in participants with primary biliary cholangitis (PBC) as measured by time to the first occurrence of any of the following adjudicated events, derived as composite event endpoints of death (all-cause), liver transplant, model of end-stage liver disease (MELD) ≥15, uncontrolled ascites, or hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy, or spontaneous bacterial peritonitis; and as expanded composite event endpoints (including events mentioned above with additional events of MELD-Na ≥15, portal hypertension syndromes, progression to decompensated liver disease, and Progression to clinical evidence of portal hypertension without decompensation).

Protection of trial subjects

This study was conducted in accordance with the International Council on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the countries in which the study was conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Dec 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 61

Country: Number of subjects enrolled

Argentina: 38

Country: Number of subjects enrolled

Canada: 31

Country: Number of subjects enrolled

Australia: 16

Country: Number of subjects enrolled

Hong Kong: 9

Country: Number of subjects enrolled

Israel: 12

Country: Number of subjects enrolled

Korea, Republic of: 6

Country: Number of subjects enrolled

Switzerland: 7

Country: Number of subjects enrolled

Chile: 3

Country: Number of subjects enrolled

Brazil: 3

Country: Number of subjects enrolled

Mexico: 1

Country: Number of subjects enrolled

Turkey: 2

Country: Number of subjects enrolled

Netherlands: 11

Country: Number of subjects enrolled

Poland: 19

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

Sweden: 4

Country: Number of subjects enrolled

United Kingdom: 26

Country: Number of subjects enrolled

Austria: 1

Country: Number of subjects enrolled

Belgium: 3

Country: Number of subjects enrolled

Denmark: 9

Country: Number of subjects enrolled

Estonia: 4

Country: Number of subjects enrolled

Finland: 5

Country: Number of subjects enrolled

France: 2

Country: Number of subjects enrolled

Germany: 9

Country: Number of subjects enrolled

Hungary: 10

Country: Number of subjects enrolled

Italy: 24

Country: Number of subjects enrolled

Lithuania: 9

Worldwide total number of subjects

334

EEA total number of subjects

119

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

280

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

A total of 334 participant were randomised into the study. The study was terminated early as the Data Monitoring Committee made the recommendation to not pursue further enrollment given the lack of feasibility for this post-marketing study as designed. At termination, the study randomised <80% of planned enrollment.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Obeticholic Acid

Arm description

Participants received obeticholic acid (OCA) 5 mg for a minimum of 3 months and titrating up to 10 mg for the remainder of the study (based on tolerability and Child-Pugh [CP] Score). 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, titrating up to a maximum dose and frequency of 10 mg twice weekly based on tolerability and biochemical response for the duration of the study.

Arm type

Experimental

Investigational medicinal product name

Obeticholic Acid

Investigational medicinal product code

747-302

Other name

6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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.

Placebo

Arm description

Participants received one tablet daily (or a lower frequency depending on CP score) for the remainder of the study.

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

Participant received one tablet of placebo daily (or a lower frequency depending on CP score) for the remainder of the study.

Number of subjects in period 1	Obeticholic Acid	Placebo
Started	168	166
Completed	0	0
Not completed	168	166
Adverse event, serious fatal	9	6
Physician decision	6	17
Liver transplant	3	3
Study Terminated by Sponsor	72	61
Site closure	3	3
Consent withdrawn by subject	28	38
Initiated Commercial OCALIVA	6	8
Adverse event, non-fatal	31	19
Liver transplant waitlist	2	2
Non-compliance with study drug	3	1
Lost to follow-up	2	7
COVID-19 pandemic limitation	2	-
Early termination as subject not met criteria	1	-
Protocol deviation	-	1

Baseline characteristics

Top of page

Reporting group title

Obeticholic Acid

Reporting group description

Reporting group title

Placebo

Reporting group description

Participants received one tablet daily (or a lower frequency depending on CP score) for the remainder of the study.

Reporting group values	Obeticholic Acid	Placebo	Total
Number of subjects	168	166	334
Age categorical
Units: Subjects
Between 18 and 65 years	140	140	280
>=65 years	28	26	54
Age continuous
Units: years
arithmetic mean (standard deviation)	53.4 ± 10.28	53.9 ± 10.41	-
Gender categorical
Units: Subjects
Female	151	149	300
Male	17	17	34
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	24	18	42
Not Hispanic or Latino	138	139	277
Unknown or Not Reported	6	9	15
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	1	2	3
Asian	11	9	20
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	2	2	4
White	146	143	289
More than one race	4	1	5
Unknown or Not Reported	4	9	13

End points

Top of page

Reporting group title

Obeticholic Acid

Reporting group description

Reporting group title

Placebo

Reporting group description

Participants received one tablet daily (or a lower frequency depending on CP score) for the remainder of the study.

Subject analysis set title

Obeticholic Acid (ITT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Intent-to-Treat (ITT) population consisted of all randomized participants who received at least 1 dose of OCA.

Subject analysis set title

Placebo (ITT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

ITT population consisted of all randomized participants who received at least 1 dose of placebo.

Subject analysis set title

Obeticholic Acid (Safety)

Subject analysis set type

Safety analysis

Subject analysis set description

The safety population consisted of all participants who received any amount of OCA. Treatment assignment based on the treatment received before any initiation of commercial OCA.

Subject analysis set title

Placebo (Safety)

Subject analysis set type

Safety analysis

Subject analysis set description

The safety population consisted of all participants who received any amount of placebo.

Subject analysis set title

Obeticholic Acid (PK)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The pharmacokinetic (PK) population consisted of all OCA participants who had at least 1 confirmed fasted analyzable sample. Participants fasted for approximately 8 hours prior to the visit and had no major protocol deviations that potentially affected exposure levels.

Primary: Time to the First Occurrence of Composite Endpoint

Top of page

End point title

Time to the First Occurrence of Composite Endpoint

End point description

To assess the effect of OCA, compared to placebo in conjunction with the established local standard of care, on clinical outcomes in participants with PBC as measured by time to the first occurrence of any of the following adjudicated events, derived as a composite event endpoint of death, liver transplant, model of end-stage liver disease (MELD) ≥15, uncontrolled ascites, or hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy (as defined by a West Haven score of >=2), or spontaneous bacterial peritonitis. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% confidence intervals (CIs) for the clinical events distribution percentiles (25th and 50th) are provided. Here 9999 represents the data that was not calculable due to insufficient clinical events. The 95% CI limits were not estimable due to an insufficient number of participants with clinical events, as indicated by 9999.

End point type

Primary

End point timeframe

Time to accrue approximately 127 primary endpoint events, up to End of Study (EOS)

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: days
number (confidence interval 95%)
25th Percentile	1092 (670 to 1464)	970 (688 to 1342)
50th Percentile	9999 (1910 to 9999)	9999 (9999 to 9999)

Time to the First Occurrence of Composite Endpoint

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.954

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.51

Primary: Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint)

Top of page

End point title

Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint)

End point description

Primary clinical outcome event is the first occurrence of the following events: death, liver transplant, MELD score >=15 (MELD-Na score >=12 baseline), MELD-Na score >=15 (MELD-Na score <12 baseline), hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis), or bacterial empyema, uncontrolled or refractory ascites (requiring large volume paracentesis), portal hypertension syndromes, progression to decompensated liver disease, and progression to clinical evidence of portal hypertension without decompensation (for participants without decompensation or clinical evidence of portal hypertension at baseline). 71 endpoint events were observed in the OCA arm, and 80 were observed in the Placebo arm. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided.

End point type

Primary

End point timeframe

Time to accrue approximately 127 primary endpoint events, up to EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168 ^[1]	166 ^[2]
Units: days
number (confidence interval 95%)
25th Percentile	370 (261 to 638)	450 (358 to 569)
50th Percentile	1827 (1198 to 9999)	1102 (841 to 9999)

Notes
[1] - 9999 = Upper 95% CI not estimated due to an insufficient number of participants with clinical events
[2] - 9999 = Upper 95% CI not estimated due to an insufficient number of participants with clinical events

Primary Clinical Event (Expanded Endpoint)

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.304

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.16

Secondary: Time to First Occurrence of Fatal Event (All-Cause)

Top of page

End point title

Time to First Occurrence of Fatal Event (All-Cause)

End point description

The results represent the ratio of OCA to placebo. The fatal events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the fatal events distribution percentiles (25th and 50th) are provided. Here 9999 represents the data that was not calculable due to insufficient clinical events. The 95% CI limits were not estimable due to an insufficient number of participants with clinical events, as indicated by 9999.

End point type

Secondary

End point timeframe

Time to first occurrence from date of randomisation until the date of death from any cause, up to EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: days
number (confidence interval 95%)
25th Percentile	9999 (9999 to 9999)	9999 (9999 to 9999)
50th Percentile	9999 (9999 to 9999)	9999 (9999 to 9999)

Time to First Occurrence Fatal Event (All-Cause)

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.568

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

2.78

Secondary: Time to First Occurrence of Liver Transplant

Top of page

End point title

Time to First Occurrence of Liver Transplant

End point description

The effect of OCA compared to placebo on time to occurrence of a liver transplant was assessed. The results represented the ratio of OCA to placebo. A hazard ratio <1 indicated an advantage for OCA. The event of interest was summarized through Cumulative Incidence Function (CIF) estimate at 5 years.

End point type

Secondary

End point timeframe

Time to first occurrence from date of randomisation until the date of first documented liver transplant or date of death from any cause, whichever came first, up to EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
number (confidence interval 95%)	0.18 (0.11 to 0.26)	0.16 (0.09 to 0.23)

Time to First Occurrence of Liver Transplant

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.769

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

2.07

Secondary: Time to First Occurrence of Hospitalization Due to Hepatic Events

Top of page

End point title

Time to First Occurrence of Hospitalization Due to Hepatic Events

End point description

Hospitalization events include new onset or recurrent variceal bleed, hepatic encephalopathy (as defined by a West Haven score of >=2), spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis OR presence of >250/mm^3 polymorph leucocytes [PMNs] in the ascitic fluid), bacterial empyema is confirmed by diagnostic thoracentesis OR presence of >250/mm^3 PMNs in the pleural fluid. The event of interest was summarized through CIF estimate at 5 years.

End point type

Secondary

End point timeframe

Time to first occurrence from date of randomisation until the date of hospitalization, liver transplant or death from any cause, whichever came first, up to EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
number (confidence interval 95%)	0.11 (0.06 to 0.17)	0.18 (0.10 to 0.26)

Occurrence of Hospitalization Due to Hepatic Event

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.599

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.67

Secondary: Time to First Occurrence of Uncontrolled or Refractory Ascites

Top of page

End point title

Time to First Occurrence of Uncontrolled or Refractory Ascites

End point description

Uncontrolled or refractory ascites are defined as diuretic-resistant ascites requiring large-volume paracentesis. The effect of OCA compared to placebo on time to the first occurrence of uncontrolled or refractory ascites was assessed. The event of interest was summarized through CIF estimate at 5 years.

End point type

Secondary

End point timeframe

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 EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
number (confidence interval 95%)	0.02 (0.01 to 0.05)	0.04 (0.01 to 0.08)

Occurrence of Uncontrolled or Refractory Ascites

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.745

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.18

upper limit

3.43

Secondary: Time to First Occurrence of MELD Score ≥15

Top of page

End point title

Time to First Occurrence of MELD Score ≥15

End point description

The MELD score is useful in assessing participants with significant decompensation, and the MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant’s serum total bilirubin, serum creatinine, and International Normalized Ratio (INR), as appropriate, to predict survival. The event of interest was summarized through CIF estimate at 5 years.

End point type

Secondary

End point timeframe

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 EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
number (confidence interval 95%)	0.13 (0.07 to 0.19)	0.18 (0.11 to 0.25)

Time to First Occurrence of MELD Score ≥15

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.437

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

1.44

Secondary: Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint

Top of page

End point title

Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint

End point description

The first occurrence of the key secondary clinical event refers to the first occurrence of the following events: death, liver transplant, MELD-Na score >=15 if MELD-Na< 12 at baseline, MELD score >=15 if MELD-Na >=12 at baseline, uncontrolled or refractory ascites, portal hypertension syndromes (hepatorenal syndrome, portopulmonary syndrome, hepatopulmonary syndrome) or hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis, or bacterial empyema. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided. Here 9999 represents the data that was not calculable due to insufficient clinical events. The 95% CI limits were not estimable due to an insufficient number of participants with clinical events, as indicated by 9999.

End point type

Secondary

End point timeframe

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 EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: days
number (confidence interval 95%)
25th Percentile	1092 (670 to 1408)	929 (679 to 1342)
50th Percentile	9999 (1910 to 9999)	9999 (9999 to 9999)

Severe Decompensating Events Expanded Composite

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.898

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.52

Secondary: Time To Liver Transplant Or Death (All-Cause)

Top of page

End point title

Time To Liver Transplant Or Death (All-Cause)

End point description

The effect of OCA compared to placebo on time to liver transplant or death (all-cause) was assessed. The events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided. Here 9999 represents the data that was not calculable due to insufficient clinical events. The 95% CI limits were not estimable due to an insufficient number of participants with clinical events, as indicated by 9999

End point type

Secondary

End point timeframe

Time to first occurrence from date of randomisation until the date of first documented liver transplant or date of death from any cause, whichever came first, up to EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: days
number (confidence interval 95%)
25th Percentile	1580 (1275 to 9999)	1803 (1206 to 9999)
50th Percentile	9999 (9999 to 9999)	9999 (9999 to 9999)

Time To Liver Transplant Or Death (All-cause)

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.594

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.91

Secondary: Time To Development Of Varix/Varices

Top of page

End point title

Time To Development Of Varix/Varices

End point description

The effect of OCA compared to placebo on time to development of varix/varices was assessed. The event of interest was summarized through CIF estimate at 5 years.

End point type

Secondary

End point timeframe

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 EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
number (confidence interval 95%)	0.07 (0.03 to 0.12)	0.09 (0.04 to 0.17)

Time To Development Of Varix/Varices

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.838

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

2.24

Secondary: Time To Liver-Related Death

Top of page

End point title

Time To Liver-Related Death

End point description

The effect of OCA compared to placebo on time to liver-related death was assessed. The event of interest was summarized through CIF estimate at 5 years.

End point type

Secondary

End point timeframe

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 EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
number (confidence interval 95%)	0.03 (0.01 to 0.07)	0.04 (0.01 to 0.09)

Time To Liver-Related Death

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.98

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

4.04

Secondary: Time To Liver-Related Death Or Liver Transplant

Top of page

End point title

Time To Liver-Related Death Or Liver Transplant

End point description

The effect of OCA compared to placebo on time to liver-related death or liver transplant was assessed. The event of interest was summarized through CIF estimate at 5 years.

End point type

Secondary

End point timeframe

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 EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
number (confidence interval 95%)	0.20 (0.13 to 0.29)	0.19 (0.12 to 0.27)

Time To Liver-Related Death Or Liver Transplant

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.933

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.83

Secondary: Time To Liver-Related Death, Liver Transplant, Or MELD Score ≥15

Top of page

End point title

Time To Liver-Related Death, Liver Transplant, Or MELD Score ≥15

End point description

The effect of OCA compared to placebo on time to liver-related death, liver transplant, or MELD Score ≥15 was assessed. The event of interest was summarized through CIF estimate at 5 years.

End point type

Secondary

End point timeframe

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 EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
number (confidence interval 95%)	0.25 (0.17 to 0.33)	0.29 (0.21 to 0.37)

Liver-related death, transplant, MELD Score ≥15

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.468

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.34

Secondary: Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline)

Top of page

End point title

Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline)

End point description

When a participant is identified as noncirrhotic at the Baseline and exhibited any signs or symptoms associated with progression to cirrhosis, the participant was assessed by Fibroscan® TE where available. The event of interest was summarized through CIF estimate at 5 years.

End point type

Secondary

End point timeframe

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 EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	78	62
Units: score on a scale
number (confidence interval 95%)	0.07 (0.02 to 0.16)	0.15 (0.06 to 0.27)

Progression To Cirrhosis (Noncirrhotic Subject)

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.19

Method

Cochran-Mantel-Haenszel

Parameter type

Hazard ratio (HR)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.13

upper limit

1.41

Progression To Cirrhosis (Noncirrhotic Subject)

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.178

Method

Gray’s Test

Parameter type

Hazard ratio (HR)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.13

upper limit

1.41

Secondary: Time To Occurrence Of Hepatocellular Carcinoma (HCC)

Top of page

End point title

Time To Occurrence Of Hepatocellular Carcinoma (HCC)

End point description

The effect of OCA compared to placebo on time to occurrence of HCC was assessed. The event of interest was summarized through CIF estimate at 5 years. Here 9999 represents the data that was not calculable due to insufficient clinical events. The 95% CI limits were not estimable due to an insufficient number of participants with clinical events, as indicated by 9999.

End point type

Secondary

End point timeframe

Time to first occurrence from date of randomisation until the date of HCC diagnosis, liver transplant or death from any cause, whichever came first, up to EOS

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168 ^[3]	166
Units: score on a scale
number (confidence interval 95%)	9999 (9999 to 9999)	0.01 (0 to 0.05)

Notes
[3] - 9999 = 95% CI limits not estimated due to an insufficient number of participants with clinical event

Time To Occurrence Of Hepatocellular Carcinoma

Comparison groups

Obeticholic Acid (ITT) v Placebo (ITT)

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.443

Method

Gray's Test

Parameter type

Hazard ratio (HR)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

3.54

Secondary: Change From Baseline To Month 24 Of Total Bilirubin

Top of page

End point title

Change From Baseline To Month 24 Of Total Bilirubin

End point description

Liver biochemistry, which includes total bilirubin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using mixed model repeated measures (MMRM), including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the interactive web review board (IWRS) as fixed effects and baseline values as a covariate. Month 6: OCA (n=149); Placebo (n=153) Month 12: OCA (n=126); Placebo (n=138) Month 24: OCA (n=97); Placebo (n=101)

End point type

Secondary

End point timeframe

Baseline up to Month 24

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: mg/dL
least squares mean (standard error)
Month 6	0.10 ± 0.069	0.17 ± 0.069
Month 12	0.26 ± 0.113	0.29 ± 0.111
Month 24	0.30 ± 0.141	0.63 ± 0.138

No statistical analyses for this end point

Secondary: Change From Baseline To Month 24 Of Direct Bilirubin

Top of page

End point title

Change From Baseline To Month 24 Of Direct Bilirubin

End point description

Liver biochemistry, which includes direct bilirubin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate. Month 6: OCA (n=147); Placebo (n=147) Month 12: OCA (n=121); Placebo (n=138) Month 24: OCA (n=96); Placebo (n=97)

End point type

Secondary

End point timeframe

Baseline up to Month 24

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: mg/dL
least squares mean (standard error)
Month 6	0.11 ± 0.054	0.14 ± 0.054
Month 12	0.13 ± 0.073	0.22 ± 0.071
Month 24	0.19 ± 0.107	0.48 ± 0.106

No statistical analyses for this end point

Secondary: Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST)

Top of page

End point title

Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST)

End point description

Liver biochemistry, which includes AST, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate. Month 6: OCA (n=147); Placebo (n=150) Month 12: OCA (n=124); Placebo (n=138) Month 24: OCA (n=97); Placebo (n=102)

End point type

Secondary

End point timeframe

Baseline up to Month 24

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: U/L
least squares mean (standard error)
Month 6	-14.5 ± 2.21	-0.6 ± 2.19
Month 12	-11.8 ± 2.36	-5.4 ± 2.27
Month 24	-14.8 ± 2.78	-6.0 ± 2.72

No statistical analyses for this end point

Secondary: Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT)

Top of page

End point title

Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT)

End point description

Liver biochemistry, which includes ALT, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate. Month 6: OCA (n=149); Placebo (n=153) Month 12: OCA (n=126); Placebo (n=138) Month 24: OCA (n=97); Placebo (n=100)

End point type

Secondary

End point timeframe

Baseline up to Month 24

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: U/L
least squares mean (standard error)
Month 6	-24.3 ± 2.62	-7.4 ± 2.59
Month 12	-20.5 ± 3.49	-12.8 ± 3.37
Month 24	-28.5 ± 2.92	-19.4 ± 2.87

No statistical analyses for this end point

Secondary: Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP)

Top of page

End point title

Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP)

End point description

Liver biochemistry, which includes ALP, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate. Month 6: OCA (n=150); Placebo (n=152) Month 12: OCA (n=126); Placebo (n=138) Month 24: OCA (n=98); Placebo (n=102)

End point type

Secondary

End point timeframe

Baseline up to Month 24

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: U/L
least squares mean (standard error)
Month 6	-134.3 ± 10.86	-37.4 ± 10.85
Month 12	-144.8 ± 12.05	-68.8 ± 11.72
Month 24	-156.4 ± 14.93	-113.1 ± 14.60

No statistical analyses for this end point

Secondary: Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT)

Top of page

End point title

Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT)

End point description

Liver biochemistry, which includes GGT, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate. Month 6: OCA (n=150); Placebo (n=152) Month 12: OCA (n=126); Placebo (n=138) Month 24: OCA (n=98); Placebo (n=102)

End point type

Secondary

End point timeframe

Baseline up to Month 24

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: U/L
least squares mean (standard error)
Month 6	-155.5 ± 15.04	-47.0 ± 14.99
Month 12	-152.2 ± 18.24	-63.4 ± 17.71
Month 24	-175.6 ± 22.49	-127.7 ± 22.04

No statistical analyses for this end point

Secondary: Change From Baseline To Month 24 Of Albumin

Top of page

End point title

Change From Baseline To Month 24 Of Albumin

End point description

Liver biochemistry, which includes albumin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate. Month 6: OCA (n=150); Placebo (n=153) Month 12: OCA (n=126); Placebo (n=138) Month 24: OCA (n=98); Placebo (n=102)

End point type

Secondary

End point timeframe

Baseline up to Month 24

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: g/L
least squares mean (standard error)
Month 6	-0.4 ± 0.19	-0.1 ± 0.19
Month 12	-0.3 ± 0.23	-0.3 ± 0.22
Month 24	-0.1 ± 0.29	-1.1 ± 0.28

No statistical analyses for this end point

Secondary: Change From Baseline To Month 24 Of INR

Top of page

End point title

Change From Baseline To Month 24 Of INR

End point description

The coagulation test, which includes INR, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate. Month 6: OCA (n=148); Placebo (n=146) Month 12: OCA (n=124); Placebo (n=136) Month 24: OCA (n=93); Placebo (n=98)

End point type

Secondary

End point timeframe

Baseline up to Month 24

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: units on a scale
least squares mean (standard error)
Month 6	0.02 ± 0.014	0.02 ± 0.014
Month 12	0.01 ± 0.009	0.02 ± 0.008
Month 24	0.03 ± 0.014	0.06 ± 0.014

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of MELD Score

Top of page

End point title

Change From Baseline To Month 72 Of MELD Score

End point description

The MELD score is useful in assessing participants with significant decompensation, and the MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant’s serum total bilirubin, serum creatinine, and INR, as appropriate, to predict survival. Month 12: OCA (n=121); Placebo (n=134) Month 24: OCA (n=91); Placebo (n=97) Month 36: OCA (n=71); Placebo (n=59) Month 48: OCA (n=48); Placebo (n=34) Month 60: OCA (n=31); Placebo (n=20) Month 72: OCA (n=7); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
median (inter-quartile range (Q1-Q3))
Month 12	0 (-0.60 to 0.60)	0 (-0.50 to 1.30)
Month 24	0 (-1.00 to 0.70)	0.20 (-0.50 to 1.70)
Month 36	0 (-1.00 to 0.50)	0.60 (-0.50 to 2.90)
Month 48	0 (-0.95 to 1.45)	0.40 (-0.80 to 1.60)
Month 60	0 (-1.30 to 0.40)	0 (-1.20 to 1.85)
Month 72	0 (-0.80 to 5.20)	1.95 (-1.40 to 3.10)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of MELD-Na Score

Top of page

End point title

Change From Baseline To Month 72 Of MELD-Na Score

End point description

The MELD score is useful in assessing participants with significant decompensation, and the MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant’s serum total bilirubin, serum creatinine, and INR, as appropriate, to predict survival. Month 12: OCA (n=121); Placebo (n=132) Month 24: OCA (n=91); Placebo (n=97) Month 36: OCA (n=71); Placebo (n=59) Month 48: OCA (n=48); Placebo (n=34) Month 60: OCA (n=31); Placebo (n=20) Month 72: OCA (n=6); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
median (inter-quartile range (Q1-Q3))
Month 12	0 (-1.0 to 0.0)	0 (-1.0 to 1.0)
Month 24	0 (-2.0 to 0)	0 (-1.0 to 1.0)
Month 36	0 (-2.0 to 0)	0 (-1.0 to 2.0)
Month 48	0 (-2.0 to 2.0)	0 (-2.0 to 2.0)
Month 60	-1.0 (-3.0 to 0)	0 (-2.5 to 1.5)
Month 72	0 (-2.0 to 0)	0.5 (-3.5 to 1.5)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of CP Score

Top of page

End point title

Change From Baseline To Month 72 Of CP Score

End point description

Child-Pugh Score (Pugh 1973, Lucey 1997) was calculated and reported within the electronic data capture (EDC) system based on data entered into the CRF by adding the scores from the 5 factors and could have ranged from 5 to15. A total score of 5 to 6 was considered Grade A (mild, well-compensated disease); 7 to 9 was Grade B (moderate, significant functional compromise); and 10 and above was Grade C (severe, decompensated disease). Month 12: OCA (n=126); Placebo (n=135) Month 24: OCA (n=93); Placebo (n=97) Month 36: OCA (n=71); Placebo (n=57) Month 48: OCA (n=47); Placebo (n=35) Month 60: OCA (n=31); Placebo (n=20) Month 72: OCA (n=7); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
median (inter-quartile range (Q1-Q3))
Month 12	0 (0 to 0)	0 (0 to 1.0)
Month 24	0 (0 to 0)	0 (0 to 1.0)
Month 36	0 (0 to 0)	0 (0 to 1.0)
Month 48	0 (0 to 0)	0 (0 to 1.0)
Month 60	0 (0 to 0)	0 (0 to 1.0)
Month 72	0 (0 to 2.0)	1.0 (0 to 1.0)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of Mayo Risk Score (MRS)

Top of page

End point title

Change From Baseline To Month 72 Of Mayo Risk Score (MRS)

End point description

Mayo Risk Score (MRS) was calculated and reported within the EDC system. Calculation of MRS included Investigator assessment of peripheral edema and the use of diuretic therapy, which was assessed during the adverse event and concomitant medicine review at the scheduled visits and entered into the CRF, as well as total bilirubin, albumin, and prothrombin time results obtained from the central laboratory data. Month 12: OCA (n=117); Placebo (n=128) Month 24: OCA (n=80); Placebo (n=91) Month 36: OCA (n=65); Placebo (n=53) Month 48: OCA (n=43); Placebo (n=29) Month 60: OCA (n=28); Placebo (n=18) Month 72: OCA (n=6); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
median (inter-quartile range (Q1-Q3))
Month 12	0 (-0.380 to 0.320)	0.080 (-0.205 to 0.535)
Month 24	-0.080 (-0.270 to 0.390)	0.140 (-0.170 to 0.660)
Month 36	-0.040 (-0.410 to 0.280)	0.050 (-0.240 to 0.650)
Month 48	0.030 (-0.430 to 0.620)	0.210 (-0.240 to 0.810)
Month 60	-0.145 (-0.575 to 0.160)	-0.060 (-0.490 to 0.790)
Month 72	-0.130 (-0.460 to 0.320)	0.990 (0.240 to 1.165)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of Immunoglobulin-M (IgM)

Top of page

End point title

Change From Baseline To Month 72 Of Immunoglobulin-M (IgM)

End point description

Markers of inflammation, which include IgM, were assessed. Month 12: OCA (n=124); Placebo (n=135) Month 24: OCA (n=97); Placebo (n=101) Month 36: OCA (n=72); Placebo (n=59) Month 48: OCA (n=48); Placebo (n=35) Month 60: OCA (n=32); Placebo (n=21) Month 72: OCA (n=7); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: g/L
median (inter-quartile range (Q1-Q3))
Month 12	-0.305 (-0.955 to 0.025)	-0.160 (-0.720 to 0.200)
Month 24	-0.470 (-1.250 to -0.090)	-0.230 (-0.630 to 0.170)
Month 36	-0.700 (-1.440 to -0.025)	-0.330 (-1.270 to 0)
Month 48	-0.525 (-1.615 to 0.005)	-0.690 (-1.540 to 0.090)
Month 60	-0.745 (-1.545 to -0.075)	-0.350 (-1.050 to -0.150)
Month 72	-1.590 (-4.100 to 0.050)	-0.640 (-1.060 to 0.645)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of C-reactive Protein (CRP)

Top of page

End point title

Change From Baseline To Month 72 Of C-reactive Protein (CRP)

End point description

Markers of inflammation, which include CRP, were assessed. Month 12: OCA (n=127); Placebo (n=137) Month 24: OCA (n=98); Placebo (n=101) Month 36: OCA (n=74); Placebo (n=59) Month 48: OCA (n=51); Placebo (n=36) Month 60: OCA (n=33); Placebo (n=22) Month 72: OCA (n=7); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: mg/L
median (inter-quartile range (Q1-Q3))
Month 12	-0.140 (-1.320 to 1.360)	0.400 (-0.760 to 2.720)
Month 24	-0.280 (-1.210 to 1.110)	0.290 (-1.450 to 2.950)
Month 36	-0.525 (-2.160 to 0.630)	0.340 (-1.460 to 3.830)
Month 48	-0.260 (-1.700 to 2.180)	-0.180 (-1.200 to 2.025)
Month 60	-0.720 (-3.020 to 0.740)	-0.730 (-2.700 to 1.650)
Month 72	-0.100 (-2.740 to 2.570)	0.765 (-2.630 to 4.715)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of Tumor Necrosis Factor-α (TNF-α)

Top of page

End point title

Change From Baseline To Month 72 Of Tumor Necrosis Factor-α (TNF-α)

End point description

Markers of inflammation, which include TNF-α, were assessed. Month 12: OCA (n=117); Placebo (n=123) Month 24: OCA (n=91); Placebo (n=95) Month 36: OCA (n=66); Placebo (n=56) Month 48: OCA (n=46); Placebo (n=33) Month 60: OCA (n=29); Placebo (n=19) Month 72: OCA (n=6); Placebo (n=3)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: pg/mL
median (inter-quartile range (Q1-Q3))
Month 12	0 (-0.362 to 0.580)	0.058 (-0.236 to 0.791)
Month 24	0.203 (-0.213 to 0.758)	0.323 (-0.039 to 0.654)
Month 36	0.055 (-0.304 to 0.627)	0.296 (-0.078 to 0.750)
Month 48	0.165 (-0.195 to 0.814)	0.539 (0.113 to 0.918)
Month 60	-0.009 (-0.765 to 0.596)	0.419 (-0.153 to 0.753)
Month 72	0.046 (-0.390 to 0.175)	0.616 (-1.318 to 0.788)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19)

Top of page

End point title

Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19)

End point description

Markers of hepatic fibrosis, which include FGF-19, were assessed. Month 12: OCA (n=124); Placebo (n=132) Month 24: OCA (n=95); Placebo (n=97) Month 36: OCA (n=69); Placebo (n=59) Month 48: OCA (n=47); Placebo (n=34) Month 60: OCA (n=31); Placebo (n=22) Month 72: OCA (n=5); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: pg/mL
median (inter-quartile range (Q1-Q3))
Month 12	73.50 (2.85 to 208.00)	-2.80 (-57.65 to 36.50)
Month 24	72.00 (1.00 to 211.00)	-0.40 (-63.00 to 61.40)
Month 36	39.90 (-17.70 to 132.00)	-2.00 (-51.00 to 50.80)
Month 48	56.00 (-24.00 to 219.00)	-9.45 (-59.90 to 39.30)
Month 60	14.40 (-30.00 to 183.00)	-1.45 (-83.40 to 156.00)
Month 72	-106.90 (-172.30 to -1.00)	-62.00 (-239.00 to -26.50)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18)

Top of page

End point title

Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18)

End point description

Markers of inflammation, which include CK-18, were assessed. Month 12: OCA (n=126); Placebo (n=133) Month 24: OCA (n=97); Placebo (n=100) Month 36: OCA (n=72); Placebo (n=59) Month 48: OCA (n=50); Placebo (n=35) Month 60: OCA (n=33); Placebo (n=21) Month 72: OCA (n=7); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: U/L
median (inter-quartile range (Q1-Q3))
Month 12	-34.450 (-138.010 to 45.800)	9.100 (-78.540 to 123.770)
Month 24	-57.660 (-158.960 to 8.470)	17.545 (-54.630 to 165.835)
Month 36	-45.935 (-171.225 to 18.715)	6.680 (-112.010 to 76.110)
Month 48	-81.035 (-158.900 to 33.550)	0.290 (-130.710 to 79.410)
Month 60	-117.660 (-232.770 to 0)	-56.390 (-159.780 to 77.020)
Month 72	-182.590 (-207.020 to 17.060)	-32.745 (-199.555 to 78.070)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of 7α-hydroxy-4-cholesten-3-one (C4)

Top of page

End point title

Change From Baseline To Month 72 Of 7α-hydroxy-4-cholesten-3-one (C4)

End point description

Markers of hepatic fibrosis, which include C4, were assessed. Month 12: OCA (n=116); Placebo (n=132) Month 24: OCA (n=96); Placebo (n=98) Month 36: OCA (n=71); Placebo (n=60) Month 48: OCA (n=49); Placebo (n=34) Month 60: OCA (n=33); Placebo (n=22) Month 72: OCA (n=7); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: ng/mL
median (inter-quartile range (Q1-Q3))
Month 12	-2.222 (-8.110 to 0.002)	-0.250 (-2.691 to 1.523)
Month 24	-3.700 (-10.119 to -0.885)	-0.861 (-5.500 to 0.900)
Month 36	-3.826 (-9.380 to 0.182)	-1.225 (-5.620 to 1.161)
Month 48	-4.220 (-9.870 to 0)	-1.168 (-12.240 to 1.691)
Month 60	-3.250 (-10.334 to -0.110)	-1.161 (-9.591 to 0.660)
Month 72	-7.500 (-10.914 to -0.690)	-0.947 (-15.281 to -0.277)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF)

Top of page

End point title

Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF)

End point description

Liver fibrosis was assessed using ELF test. The ELF test assessed: hyaluronic acid, procollagen3 N-terminal peptide, and a tissue inhibitor of metalloproteinase 1. Month 12: OCA (n=126); Placebo (n=127) Month 24: OCA (n=95); Placebo (n=95) Month 36: OCA (n=71); Placebo (n=59) Month 48: OCA (n=48); Placebo (n=34) Month 60: OCA (n=33); Placebo (n=21) Month 72: OCA (n=7); Placebo (n=4)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: score on a scale
median (inter-quartile range (Q1-Q3))
Month 12	0.10 (-0.50 to 0.60)	0.10 (-0.20 to 0.70)
Month 24	0 (-0.70 to 0.60)	0.20 (-0.40 to 1.00)
Month 36	-0.20 (-0.90 to 0.70)	0 (-0.60 to 0.70)
Month 48	0.25 (-0.45 to 0.80)	0.10 (-0.70 to 1.10)
Month 60	-0.20 (-1.20 to 0.60)	0.10 (-1.00 to 1.00)
Month 72	0 (-0.80 to 2.80)	-0.20 (-1.10 to 0.45)

No statistical analyses for this end point

Secondary: Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography

Top of page

End point title

Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography

End point description

Hepatic stiffness was measured using non-invasive transient Elastography with a Fibroscan® TE device. Month 12: OCA (n=88); Placebo (n=90) Month 24: OCA (n=67); Placebo (n=67) Month 36: OCA (n=49); Placebo (n=41) Month 48: OCA (n=31); Placebo (n=19) Month 60: OCA (n=19); Placebo (n=14) Month 72: OCA (n=5); Placebo (n=3)

End point type

Secondary

End point timeframe

Baseline up to Month 72

End point values	Obeticholic Acid (ITT)	Placebo (ITT)
Number of subjects analysed	168	166
Units: kPa
median (inter-quartile range (Q1-Q3))
Month 12	0.25 (-2.40 to 4.05)	0.90 (-1.80 to 7.30)
Month 24	-0.60 (-2.60 to 3.60)	1.50 (-2.20 to 15.60)
Month 36	0.30 (-3.40 to 5.50)	2.00 (-1.60 to 9.10)
Month 48	0.70 (-2.20 to 4.00)	1.00 (-2.80 to 11.90)
Month 60	0.20 (-2.50 to 6.00)	-1.35 (-4.70 to 1.90)
Month 72	-2.40 (-2.50 to 2.70)	3.20 (-2.20 to 8.70)

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as AEs that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the ‘Reported Adverse Events’ Section.

End point type

Secondary

End point timeframe

Baseline up to the last IP dose plus 30 days and prior to commercial OCA initiation date

End point values	Obeticholic Acid (Safety)	Placebo (Safety)
Number of subjects analysed	168	166
Units: participants
TEAEs	162	158
SAE	53	53

No statistical analyses for this end point

Secondary: Pharmacokinetic (PK) Population: Fasting Trough Concentrations Of OCA By Dose Regimen

Top of page

End point title

Pharmacokinetic (PK) Population: Fasting Trough Concentrations Of OCA By Dose Regimen

End point description

The fasting trough PK concentrations of OCA of different dose regimens taken throughout the study are reported. Here 9999 represents data that were not available.

End point type

Secondary

End point timeframe

Months 3, 6, 9, 12, 24, 36, 48, and 60

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149
Units: ng/mL
geometric mean (geometric coefficient of variation)
5 mg QD (Month 3)	119 ± 185
5 mg QD (Month 6)	102 ± 186
5 mg QD (Month 9)	175 ± 33.0
5 mg QD (Month 12)	117 ± 153
5 mg QD (Month 24)	113 ± 121
5 mg QD (Month 36)	84.5 ± 169
5 mg QD (Month 48)	203 ± 181
5 mg QD (Month 60)	7.96 ± 173
5 mg QOD (Month 3)	123 ± 191
5 mg QOD (Month 6)	103 ± 232
5 mg QOD (Month 9)	396 ± 9999
5 mg QOD (Month 12)	103 ± 97.2
5 mg QOD (Month 24)	134 ± 17.1
5 mg QOD (Month 48)	307 ± 9999
5 mg QW (Month 3)	57.3 ± 199
5 mg QW (Month 6)	31.0 ± 125
5 mg QW (Month 12)	73.5 ± 302
5 mg QW (Month 24)	171 ± 109
5 mg QW (Month 36)	245 ± 34.8
5 mg QW (Month 48)	141 ± 216
5 mg Q2W (Month 3)	61.9 ± 54.7
5 mg Q2W (Month 6)	108 ± 57.1
5 mg Q2W (Month 12)	187 ± 30.8
5 mg Q2W (Month 24)	208 ± 61.0
5 mg Q2W (Month 36)	225 ± 159
5 mg Q2W (Month 48)	502 ± 59.6
5 mg Q2W (Month 60)	7.32 ± 9999
5 mg other regimens (Month 3)	50.3 ± 1730
5 mg other regimens (Month 6)	79.6 ± 68.2
5 mg other regimens (Month 12)	20.6 ± 500
5 mg other regimens (Month 24)	91.1 ± 236
10 mg QD (Month 6)	126 ± 161
10 mg QD (Month 9)	51.1 ± 167
10 mg QD (Month 12)	86.9 ± 188
10 mg QD (Month 24)	85.6 ± 152
10 mg QD (Month 36)	79.9 ± 143
10 mg QD (Month 48)	81.2 ± 161
10 mg QD (Month 60)	48.6 ± 323
10 mg QOD (Month 12)	102 ± 576
10 mg QOD (Month 24)	25.5 ± 9999
10 mg QOD (Month 48)	9.08 ± 9999
10 mg Q2W (Month 6)	538 ± 9999
10 mg Q2W (Month 9)	566 ± 9999
10 mg Q2W (Month 12)	41.7 ± 45.6
10 mg Q2W (Month 24)	62.5 ± 35.9
10 mg Q2W (Month 36)	96.3 ± 132
10 mg Q2W (Month 48)	70.9 ± 218
10 mg Q2W (Month 60)	83.8 ± 9999
10 mg Q3D (Month 12)	0.861 ± 9999

No statistical analyses for this end point

Secondary: PK Population: Serial Concentration of OCA By Dose Regimen

Top of page

End point title

PK Population: Serial Concentration of OCA By Dose Regimen

End point description

On Month 9, blood samples were collected at predose, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h and PK serial concentrations at different dose regimen are reported. Here 9999 represents data that were not available.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	13
Units: ng/mL
geometric mean (geometric coefficient of variation)
5 mg QD (Predose)	61.2 ± 315
5 mg QD (0.5 h)	109 ± 66.1
5 mg QD (0.75 h)	158 ± 35.6
5 mg QD (1 h)	173 ± 56.4
5 mg QD (1.5 h)	137 ± 53.2
5 mg QD (2 h)	100 ± 100
5 mg QD (2.5 h)	90.1 ± 93.0
5 mg QD (3 h)	64.7 ± 47.1
5 mg QD (4 h)	71.6 ± 179
5 mg QD (5 h)	193 ± 150
5 mg QD (6 h)	199 ± 203
5 mg QOD (Predose)	396 ± 9999
5 mg QOD (0.5 h)	236 ± 9999
5 mg QOD (0.75 h)	211 ± 9999
5 mg QOD (1 h)	217 ± 9999
5 mg QOD (1.5 h)	232 ± 9999
5 mg QOD (2 h)	243 ± 9999
5 mg QOD (2.5 h)	240 ± 9999
5 mg QOD (3 h)	171 ± 9999
5 mg QOD (4 h)	117 ± 9999
5 mg QOD (5 h)	282 ± 9999
5 mg QOD (6 h)	544 ± 9999
10 mg QD (Predose)	64.2 ± 139
10 mg QD (0.5 h)	142 ± 55.8
10 mg QD (0.75 h)	176 ± 55.5
10 mg QD (1 h)	196 ± 65.5
10 mg QD (1.5 h)	254 ± 64.0
10 mg QD (2 h)	233 ± 54.0
10 mg QD (2.5 h)	206 ± 80.2
10 mg QD (3 h)	217 ± 90.7
10 mg QD (4 h)	151 ± 74.4
10 mg QD (5 h)	180 ± 80.0
10 mg QD (6 h)	214 ± 77.9
10 mg Q2W (Predose)	370 ± 65.8
10 mg Q2W (0.5 h)	490 ± 52.6
10 mg Q2W (P0.75 h)	593 ± 68.2
10 mg Q2W (1 h)	633 ± 69.5
10 mg Q2W (1.5 h)	425 ± 9999
10 mg Q2W (2 h)	769 ± 64.5
10 mg Q2W (2.5 h)	716 ± 75.1
10 mg Q2W (3 h)	602 ± 77.2
10 mg Q2W (4 h)	422 ± 116
10 mg Q2W (5 h)	758 ± 84.4
10 mg Q2W (6 h)	728 ± 169

No statistical analyses for this end point

Secondary: 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)

Top of page

End point title

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)

End point description

On Month 9, blood samples were collected at predose, 0.5h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[4]
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	758 ± 9999

Notes
[4] - No variation was calculated.

No statistical analyses for this end point

Secondary: 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

Top of page

End point title

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

End point description

On Month 9, blood samples were collected at predose, 0.5h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[5]
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	3710 ± 9999

Notes
[5] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Maximum Observed Concentration (Cmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: Maximum Observed Concentration (Cmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: ng/mL
geometric mean (geometric coefficient of variation)	317 ± 9999

No statistical analyses for this end point

Secondary: PK Population: Time to Cmax (Tmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: Time to Cmax (Tmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: hours
median (full range (min-max))	6.0 (6.0 to 6.0)

No statistical analyses for this end point

Secondary: PK Population: Metabolite to Parent Ratio of AUC0-6h (MRAUC) Of Participants Who Received 5mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: Metabolite to Parent Ratio of AUC0-6h (MRAUC) Of Participants Who Received 5mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: units on a scale
geometric mean (geometric coefficient of variation)	15.9 ± 9999

No statistical analyses for this end point

Secondary: PK Population: Metabolite to Parent Ration of Cmax (MRCmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: Metabolite to Parent Ration of Cmax (MRCmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: units on a scale
geometric mean (geometric coefficient of variation)	8.93 ± 9999

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	889 ± 133

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	4040 ± 129

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 5mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: Cmax Of Participants Who Received 5mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: ng/mL
geometric mean (geometric coefficient of variation)	275 ± 117

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 5mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: Tmax Of Participants Who Received 5mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: hours
median (full range (min-max))	3.38 (0.750 to 6.0)

No statistical analyses for this end point

Secondary: PK Population: Concentration at 24 Hours Post-dose (Ctrough) Of Participants Who Received 5mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: Concentration at 24 Hours Post-dose (Ctrough) Of Participants Who Received 5mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: ng/mL
geometric mean (geometric coefficient of variation)	149 ± 22.2

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 5mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 5mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: units on a scale
geometric mean (geometric coefficient of variation)	8.41 ± 50.8

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 5mg QD OCA and With CP Score=B

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 5mg QD OCA and With CP Score=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: ng/mL
geometric mean (geometric coefficient of variation)	242 ± 9999

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[6]
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	1480 ± 9999

Notes
[6] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	9940 ± 9999

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC

Top of page

End point title

PK Population: Cmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[7]
Units: ng/mL
geometric mean (geometric coefficient of variation)	544 ± 9999

Notes
[7] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC

Top of page

End point title

PK Population: Tmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: hours
median (full range (min-max))	6.0 (6.0 to 6.0)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 5mg QOD OCA and With CP Score=NC

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 5mg QOD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[8]
Units: ng/mL
geometric mean (geometric coefficient of variation)	396 ± 9999

Notes
[8] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 5mg QOD OCA and With CP Score=NC

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 5mg QOD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[9]
Units: unit on a scale
geometric mean (geometric coefficient of variation)	26.6 ± 9999

Notes
[9] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[10]
Units: units on a scale
geometric mean (geometric coefficient of variation)	15.8 ± 9999

Notes
[10] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	1090 ± 98.4

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	3820 ± 91.7

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: ng/mL
geometric mean (geometric coefficient of variation)	289 ± 74.5

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: hours
median (full range (min-max))	1.50 (1.50 to 3.00)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	4
Units: ng/mL
geometric mean (geometric coefficient of variation)	50.6 ± 148

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: units on a scale
geometric mean (geometric coefficient of variation)	13.8 ± 151

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: units on a scale
geometric mean (geometric coefficient of variation)	4.02 ± 107

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	1310 ± 11.9

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CPS Score=A

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CPS Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	4280 ± 26.1

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: ng/mL
geometric mean (geometric coefficient of variation)	334 ± 6.71

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CPS Score=A On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A. Month 9

Top of page

End point title

PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CPS Score=A On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A. Month 9

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: hours
median (full range (min-max))	1.50 (0.750 to 2.50)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: ng/mL
geometric mean (geometric coefficient of variation)	55.2 ± 414

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: units on a scale
geometric mean (geometric coefficient of variation)	2.94 ± 15.5

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=A

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=A

End point description

PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=A

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: units on a scale
geometric mean (geometric coefficient of variation)	1.48 ± 21.8

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	3770 ± 84.9

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	13900 ± 113

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

Top of page

End point title

PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: ng/mL
geometric mean (geometric coefficient of variation)	916 ± 101

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

Top of page

End point title

PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: hour
median (full range (min-max))	4.0 (2.0 to 6.0)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[11]
Units: ng/mL
geometric mean (geometric coefficient of variation)	566 ± 9999

Notes
[11] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: units on a scale
geometric mean (geometric coefficient of variation)	12.6 ± 450

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: units on a scale
geometric mean (geometric coefficient of variation)	7.13 ± 315

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	1170 ± 68.0

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	5490 ± 60.2

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: ng/mL
geometric mean (geometric coefficient of variation)	410 ± 37.4

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: hour
median (full range (min-max))	6.0 (6.0 to 6.0)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[12]
Units: ng/mL
geometric mean (geometric coefficient of variation)	174 ± 9999

Notes
[12] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: units on a scale
geometric mean (geometric coefficient of variation)	13.7 ± 21.1

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: units on a scale
geometric mean (geometric coefficient of variation)	7.15 ± 32.3

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[13]
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	436 ± 9999

Notes
[13] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[14]
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	2000 ± 9999

Notes
[14] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[15]
Units: ng/mL
geometric mean (geometric coefficient of variation)	143 ± 9999

Notes
[15] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: hour
median (full range (min-max))	0.750 (0.750 to 0.750)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: ng/mL
geometric mean (geometric coefficient of variation)	176 ± 47.9

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[16]
Units: units on a scale
geometric mean (geometric coefficient of variation)	5.99 ± 9999

Notes
[16] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[17]
Units: units on a scale
geometric mean (geometric coefficient of variation)	2.48 ± 9999

Notes
[17] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[18]
Units: units on a scale
geometric mean (geometric coefficient of variation)	1480 ± 9999

Notes
[18] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[19]
Units: units on a scale
geometric mean (geometric coefficient of variation)	9940 ± 9999

Notes
[19] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

Top of page

End point title

PK Population: Cmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[20]
Units: units on a scale
geometric mean (geometric coefficient of variation)	544 ± 9999

Notes
[20] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

Top of page

End point title

PK Population: Tmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1
Units: hour
median (full range (min-max))	6.0 (6.0 to 6.0)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[21]
Units: ng/mL
geometric mean (geometric coefficient of variation)	396 ± 9999

Notes
[21] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[22]
Units: units on a scale
geometric mean (geometric coefficient of variation)	26.6 ± 9999

Notes
[22] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[23]
Units: units on a scale
geometric mean (geometric coefficient of variation)	15.8 ± 9999

Notes
[23] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=A

End point description

PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=A

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	886 ± 55.6

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	2860 ± 35.5

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: ng/mL
geometric mean (geometric coefficient of variation)	240 ± 35.1

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: hour
median (full range (min-max))	1.50 (1.50 to 3.00)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	4
Units: ng/mL
geometric mean (geometric coefficient of variation)	25.8 ± 188

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: units on a scale
geometric mean (geometric coefficient of variation)	6.04 ± 162

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: units on a scale
geometric mean (geometric coefficient of variation)	1.92 ± 50.6

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	1610 ± 44.6

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=B

End point description

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	5700 ± 48.7

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: ng/mL
geometric mean (geometric coefficient of variation)	403 ± 39.4

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: hours
median (full range (min-max))	1.50 (0.750 to 2.50)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: ng/mL
geometric mean (geometric coefficient of variation)	136 ± 14.9

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: units on a scale
geometric mean (geometric coefficient of variation)	6.73 ± 212

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	3
Units: units on a scale
geometric mean (geometric coefficient of variation)	3.11 ± 147

No statistical analyses for this end point

Secondary: PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

Top of page

End point title

PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	3770 ± 84.9

No statistical analyses for this end point

Secondary: PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

Top of page

End point title

PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	13900 ± 113

No statistical analyses for this end point

Secondary: PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

Top of page

End point title

PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: ng/mL
geometric mean (geometric coefficient of variation)	916 ± 101

No statistical analyses for this end point

Secondary: PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

Top of page

End point title

PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: hour
median (full range (min-max))	4.0 (2.0 to 6.0)

No statistical analyses for this end point

Secondary: PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

Top of page

End point title

PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[24]
Units: ng/mL
geometric mean (geometric coefficient of variation)	566 ± 9999

Notes
[24] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

Top of page

End point title

PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: units on a scale
geometric mean (geometric coefficient of variation)	12.6 ± 450

No statistical analyses for this end point

Secondary: PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

Top of page

End point title

PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B

End point description

On Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.

End point type

Secondary

End point timeframe

Month 9

End point values	Obeticholic Acid (PK)
Number of subjects analysed	2
Units: units on a scale
geometric mean (geometric coefficient of variation)	7.13 ± 315

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QD OCA

Top of page

End point title

PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QD OCA

End point description

The trough concentration of OCA in the cirrhotic participants who received 5 mg QD OCA was reported.

End point type

Secondary

End point timeframe

Months 3, 6, 12, 24, and 48

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149 ^[25]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Month 3	295 ± 9999
Month 6	291 ± 166
Month 12	227 ± 127
Month 24	127 ± 9999
Month 48	849 ± 9999

Notes
[25] - No variation was calculated for Months 3, 24, and 48.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QD OCA

Top of page

End point title

PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QD OCA

End point description

The trough concentration of OCA in the non-cirrhotic participants who received 5 mg QD OCA was reported.

End point type

Secondary

End point timeframe

Months 3, 6, 9, 12, and 24

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149 ^[26]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Month 3	77.4 ± 157
Month 6	55.9 ± 85.1
Month 9	127 ± 9999
Month 12	96.0 ± 94.7
Month 24	45.4 ± 693

Notes
[26] - No variation was calculated on Month 9.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QOD OCA

Top of page

End point title

PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QOD OCA

End point description

The trough concentration of OCA in the cirrhotic participants who received 5 mg QOD OCA was reported.

End point type

Secondary

End point timeframe

Months 6, 12, and 24

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149 ^[27]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Month 6	1050 ± 9999
Month 12	48.0 ± 9999
Month 24	134 ± 17.1

Notes
[27] - No variation was calculated on Months 6 and 12.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QOD OCA

Top of page

End point title

PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QOD OCA

End point description

The trough concentration of OCA in the non-cirrhotic participants who received 5 mg QOD OCA was reported.

End point type

Secondary

End point timeframe

Months 3, 6, and 12

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149 ^[28]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Month 3	97.2 ± 53.9
Month 6	85.4 ± 9999
Month 12	200 ± 184

Notes
[28] - No variation was calculated on Month 6.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QW OCA

Top of page

End point title

PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QW OCA

End point description

The trough concentration of OCA in the cirrhotic participants who received 5 mg QW OCA was reported.

End point type

Secondary

End point timeframe

Months 6 and 12

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149 ^[29]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Month 6	56.7 ± 9999
Month 12	116 ± 395

Notes
[29] - No variation was calculated on Month 6.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QW OCA

Top of page

End point title

PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QW OCA

End point description

At month 12, the trough concentration of OCA in the non-cirrhotic participants who received 5 QW QOD OCA was reported.

End point type

Secondary

End point timeframe

Month 12

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[30]
Units: ng/mL
geometric mean (geometric coefficient of variation)	179 ± 9999

Notes
[30] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg Q2W OCA

Top of page

End point title

PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg Q2W OCA

End point description

At Month 6, the trough concentration of OCA in the cirrhotic participants who received 5 mg Q2W OCA was reported.

End point type

Secondary

End point timeframe

Month 6

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[31]
Units: ng/mL
geometric mean (geometric coefficient of variation)	131 ± 9999

Notes
[31] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg Q2W OCA

Top of page

End point title

PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg Q2W OCA

End point description

The trough concentration of OCA in the non-cirrhotic participants who received 5 Q2W QOD OCA was reported.

End point type

Secondary

End point timeframe

Months 3, 6, 12, 24, 36, and 48

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149 ^[32]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Month 3	86.0 ± 9999
Month 6	122 ± 9999
Month 12	250 ± 9999
Month 24	497 ± 9999
Month 36	117 ± 9999
Month 48	271 ± 9999

Notes
[32] - No variation was calculated at all timepoints.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QD OCA

Top of page

End point title

PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QD OCA

End point description

The trough concentration of OCA in the cirrhotic participants who received 10 mg QD OCA was reported.

End point type

Secondary

End point timeframe

Months 6, 9, 12, 24, 36, and 60

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149 ^[33]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Month 6	142 ± 242
Month 9	7.74 ± 9999
Month 12	133 ± 489
Month 24	396 ± 61.7
Month 36	346 ± 9999
Month 60	290 ± 9999

Notes
[33] - No variation was calculated on Months 9, 36, and 60.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QD OCA

Top of page

End point title

PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QD OCA

End point description

The trough concentration of OCA in the non-cirrhotic participants who received 10 QD QOD OCA was reported.

End point type

Secondary

End point timeframe

Months 6, 9, 12, 24, and 36

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149
Units: ng/mL
geometric mean (geometric coefficient of variation)
Month 6	127 ± 601
Month 9	74.5 ± 10.6
Month 12	73.3 ± 102
Month 24	100 ± 216
Month 36	98.5 ± 1730

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QOD OCA

Top of page

End point title

PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QOD OCA

End point description

The trough concentration of OCA in the Cirrhotic participants who received 10 mg QOD OCA was reported.

End point type

Secondary

End point timeframe

Months 3, 6, 9, 12, 24, 36, 48, and 60

End point values	Obeticholic Acid (PK)
Number of subjects analysed	149 ^[34]
Units: ng/mL
geometric mean (geometric coefficient of variation)	0 ± 0

Notes
[34] - No participants was tested for this outcome measure.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QOD OCA

Top of page

End point title

PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QOD OCA

End point description

At Month 12, the trough concentration of OCA in the non-cirrhotic participants who received 10 mg OCA QOD was reported.

End point type

Secondary

End point timeframe

Month 12

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[35]
Units: ng/mL
geometric mean (geometric coefficient of variation)	26.9 ± 9999

Notes
[35] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg Q2W OCA

Top of page

End point title

PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg Q2W OCA

End point description

At Month 6, the trough concentration of OCA in the cirrhotic participants who received 10 mg Q2W OCA was reported.

End point type

Secondary

End point timeframe

Month 6

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[36]
Units: ng/mL
geometric mean (geometric coefficient of variation)	538 ± 9999

Notes
[36] - No variation was calculated.

No statistical analyses for this end point

Secondary: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg Q2W OCA

Top of page

End point title

PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg Q2W OCA

End point description

At Month 6, the trough concentration of OCA in the non-cirrhotic participants who received 10 mg Q2W OCA was reported.

End point type

Secondary

End point timeframe

Month 6

End point values	Obeticholic Acid (PK)
Number of subjects analysed	1 ^[37]

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 4, Double Blind, Randomized, Placebo Controlled, Multicenter Study Evaluating the Effect of Obeticholic Acid on Clinical Outcomes in Subjects with Primary Biliary Cholangitis. The COBALT Study Clinical Outcomes with Obeticholic Acid in Liver Treatment (COBALT)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Time to the First Occurrence of Composite Endpoint

Primary: Time to the First Occurrence of Composite Endpoint

Primary: Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint)

Primary: Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint)

Secondary: Time to First Occurrence of Fatal Event (All-Cause)

Secondary: Time to First Occurrence of Fatal Event (All-Cause)

Secondary: Time to First Occurrence of Liver Transplant

Secondary: Time to First Occurrence of Liver Transplant

Secondary: Time to First Occurrence of Hospitalization Due to Hepatic Events

Secondary: Time to First Occurrence of Hospitalization Due to Hepatic Events

Secondary: Time to First Occurrence of Uncontrolled or Refractory Ascites

Secondary: Time to First Occurrence of Uncontrolled or Refractory Ascites

Secondary: Time to First Occurrence of MELD Score ≥15

Secondary: Time to First Occurrence of MELD Score ≥15

Secondary: Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint

Secondary: Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint

Secondary: Time To Liver Transplant Or Death (All-Cause)

Secondary: Time To Liver Transplant Or Death (All-Cause)

Secondary: Time To Development Of Varix/Varices

Secondary: Time To Development Of Varix/Varices

Secondary: Time To Liver-Related Death

Secondary: Time To Liver-Related Death

Secondary: Time To Liver-Related Death Or Liver Transplant

Secondary: Time To Liver-Related Death Or Liver Transplant

Secondary: Time To Liver-Related Death, Liver Transplant, Or MELD Score ≥15

Secondary: Time To Liver-Related Death, Liver Transplant, Or MELD Score ≥15

Secondary: Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline)

Secondary: Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline)

Secondary: Time To Occurrence Of Hepatocellular Carcinoma (HCC)

Secondary: Time To Occurrence Of Hepatocellular Carcinoma (HCC)

Secondary: Change From Baseline To Month 24 Of Total Bilirubin

Secondary: Change From Baseline To Month 24 Of Total Bilirubin

Secondary: Change From Baseline To Month 24 Of Direct Bilirubin

Secondary: Change From Baseline To Month 24 Of Direct Bilirubin

Secondary: Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST)

Secondary: Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST)

Secondary: Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT)

Secondary: Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT)

Secondary: Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP)

Secondary: Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP)

Secondary: Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT)

Secondary: Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT)

Secondary: Change From Baseline To Month 24 Of Albumin

Secondary: Change From Baseline To Month 24 Of Albumin

Secondary: Change From Baseline To Month 24 Of INR

Secondary: Change From Baseline To Month 24 Of INR

Secondary: Change From Baseline To Month 72 Of MELD Score

Secondary: Change From Baseline To Month 72 Of MELD Score

Secondary: Change From Baseline To Month 72 Of MELD-Na Score

Secondary: Change From Baseline To Month 72 Of MELD-Na Score

Secondary: Change From Baseline To Month 72 Of CP Score

Secondary: Change From Baseline To Month 72 Of CP Score

Secondary: Change From Baseline To Month 72 Of Mayo Risk Score (MRS)

Secondary: Change From Baseline To Month 72 Of Mayo Risk Score (MRS)

Secondary: Change From Baseline To Month 72 Of Immunoglobulin-M (IgM)

Secondary: Change From Baseline To Month 72 Of Immunoglobulin-M (IgM)

Secondary: Change From Baseline To Month 72 Of C-reactive Protein (CRP)

Secondary: Change From Baseline To Month 72 Of C-reactive Protein (CRP)

Secondary: Change From Baseline To Month 72 Of Tumor Necrosis Factor-α (TNF-α)

Secondary: Change From Baseline To Month 72 Of Tumor Necrosis Factor-α (TNF-α)

Secondary: Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19)

Secondary: Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19)

Secondary: Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18)

Secondary: Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18)

Secondary: Change From Baseline To Month 72 Of 7α-hydroxy-4-cholesten-3-one (C4)

Secondary: Change From Baseline To Month 72 Of 7α-hydroxy-4-cholesten-3-one (C4)

Secondary: Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF)

Secondary: Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF)

Secondary: Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography

Secondary: Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography

Clinical Trial Results:
A Phase 4, Double Blind, Randomized, Placebo Controlled, Multicenter Study Evaluating the Effect of Obeticholic Acid on Clinical Outcomes in Subjects with Primary Biliary Cholangitis. The COBALT Study Clinical Outcomes with Obeticholic Acid in Liver Treatment (COBALT)