Clinical Trial Results:
A Phase 4, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Pharmacokinetics and Safety of Obeticholic Acid in Patients with Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment
Summary
|
|
EudraCT number |
2017-001762-13 |
Trial protocol |
ES DE BE HU EE LT IT |
Global end of trial date |
09 Jul 2021
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
24 Jul 2022
|
First version publication date |
24 Jul 2022
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
747-401
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03633227 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Intercept Pharmaceuticals, Inc.
|
||
Sponsor organisation address |
305 Madison Avenue, Morristown, NJ, United States, 07960
|
||
Public contact |
Medical Information, Intercept Pharmaceuticals, Inc., +1 844-782-4278, medinfo@interceptpharma.com
|
||
Scientific contact |
Medical Information, Intercept Pharmaceuticals, Inc., +1 844-782-4278, medinfo@interceptpharma.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
20 Jun 2022
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
09 Jul 2021
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
To evaluate the pharmacokinetics (PK) of Obeticholic acid (OCA) and its conjugates, glycine 6α-ethyl chenodeoxycholic acid (glyco-OCA) and taurine 6α-ethyl chenodeoxycholic acid (tauro-OCA), and OCA metabolite glucuronide (OCA-glucuronide) compared with placebo. To evaluate the safety and tolerability of OCA treatment compared with placebo.
|
||
Protection of trial subjects |
The study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Council for Harmonisation (ICH)/Good Clinical Practice (GCP), applicable regulatory requirements and the Sponsor’s policies.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Jun 2018
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 2
|
||
Country: Number of subjects enrolled |
Belgium: 1
|
||
Country: Number of subjects enrolled |
Estonia: 1
|
||
Country: Number of subjects enrolled |
Germany: 1
|
||
Country: Number of subjects enrolled |
Lithuania: 2
|
||
Country: Number of subjects enrolled |
United States: 8
|
||
Country: Number of subjects enrolled |
Australia: 1
|
||
Country: Number of subjects enrolled |
Brazil: 2
|
||
Country: Number of subjects enrolled |
Argentina: 4
|
||
Worldwide total number of subjects |
22
|
||
EEA total number of subjects |
7
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
12
|
||
From 65 to 84 years |
10
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||||||||||
Recruitment details |
This study was conducted at study sites in the United States, Argentina, Belgium, Spain, Lithuania, Brazil, Australia, Germany, Estonia, Italy, Canada, and Hungary. | |||||||||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||||||||
Screening details |
A total of 31 participants were screened and 22 participants were randomized. | |||||||||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||||||||
Period 1 title |
Double Blind (DB), up to Week 48
|
|||||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||
Arm title
|
Placebo | |||||||||||||||||||||||||||||||||
Arm description |
Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks. | |||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||
Dosage and administration details |
OCA matching placebo was administered per schedule specified in the arm description.
|
|||||||||||||||||||||||||||||||||
Arm title
|
Obeticholic Acid (OCA) | |||||||||||||||||||||||||||||||||
Arm description |
Participants initiated treatment with OCA 5 milligrams (mg) tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Obeticholic Acid
|
|||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||
Dosage and administration details |
OCA was administered per dose and schedule specified in the arm description.
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Period 2
|
||||||||||||||||||||||||||||||||||
Period 2 title |
DB Extension, Week 48 up to 3 Years
|
|||||||||||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||
Arm title
|
Placebo | |||||||||||||||||||||||||||||||||
Arm description |
Participants, who had completed their 48-week treatment, could continue the treatment until all randomized participants had completed their 48-week treatment period and the database for that period was locked (total duration: approximately up to 3 years). | |||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||
Dosage and administration details |
OCA matching placebo was administered per the schedule specified in the arm description.
|
|||||||||||||||||||||||||||||||||
Arm title
|
Obeticholic Acid (OCA) | |||||||||||||||||||||||||||||||||
Arm description |
Participants, who had completed their 48-week treatment, could continue the treatment until all randomized participants had completed their 48-week treatment period and the database for that period was locked (total duration: approximately up to 3 years). | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Obeticholic Acid
|
|||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||
Dosage and administration details |
OCA was administered per dose and schedule specified in the arm description.
|
|||||||||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Obeticholic Acid (OCA)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants initiated treatment with OCA 5 milligrams (mg) tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Placebo
|
||
Reporting group description |
Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks. | ||
Reporting group title |
Obeticholic Acid (OCA)
|
||
Reporting group description |
Participants initiated treatment with OCA 5 milligrams (mg) tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Participants, who had completed their 48-week treatment, could continue the treatment until all randomized participants had completed their 48-week treatment period and the database for that period was locked (total duration: approximately up to 3 years). | ||
Reporting group title |
Obeticholic Acid (OCA)
|
||
Reporting group description |
Participants, who had completed their 48-week treatment, could continue the treatment until all randomized participants had completed their 48-week treatment period and the database for that period was locked (total duration: approximately up to 3 years). | ||
Subject analysis set title |
OCA 5 mg Once Weekly
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants received OCA 5 mg tablets orally once weekly.
|
||
Subject analysis set title |
OCA 5 mg Twice Weekly
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants received OCA 5 mg tablets orally twice weekly.
|
||
Subject analysis set title |
OCA 10 mg Twice Weekly
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants received OCA 10 mg tablets orally twice weekly.
|
||
Subject analysis set title |
Placebo
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks. Participants, who had completed their 48-Week treatment, could continue the treatment until all randomized participants had completed their 48-Week treatment period and the database for that period was locked (total duration: approximately up to 3 years).
|
||
Subject analysis set title |
Obeticholic Acid (OCA)
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Participants initiated treatment with OCA 5 mg tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks. Participants, who had completed their 48-Week treatment, could continue the treatment until all randomized participants had completed their 48-Week treatment period and the database for that period was locked (total duration: approximately up to 3 years).
|
|
|||||||||||||||||
End point title |
Maximum Observed Concentration (Cmax) of Total OCA at Week 12 [1] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Analysis population description (APD): PK Population: participants who received OCA and had adequate concentration-time profile to characterize OCA and its conjugates and must not have had any major protocol deviations that potentially affect exposure level. Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [2] - No participant started OCA 5 mg twice weekly at Week 12. [3] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Time to Maximum Concentration (Tmax) of Total OCA at Week 12 [4] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [5] - No participant started OCA 5 mg twice weekly at Week 12. [6] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Trough Concentration (Ctrough) of Total OCA at Week 12 [7] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 12. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 12
|
||||||||||||||||
Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [8] - No participant started OCA 5 mg twice weekly at week 12. [9] - No participant started OCA 10 mg twice weekly at week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Area Under the Concentration Versus Time Curve From Zero Time to 24 Hours (AUC0-24h) of Total OCA at Week 12 [10] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [11] - No participant started OCA 5 mg twice weekly at Week 12. [12] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Total OCA at Week 18 [13] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [14] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Total OCA at Week 18 [15] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [16] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Total OCA at Week 18 [17] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 18. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 18
|
||||||||||||||||
Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [18] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Total OCA at Week 18 [19] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [20] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Total OCA at Week 24 [21] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [22] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Total OCA at Week 24 [23] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Total OCA at Week 24 [24] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 24. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 24
|
||||||||||||||||
Notes [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [25] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Total OCA at Week 24 [26] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [27] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Total OCA at Week 30 [28] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [29] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Total OCA at Week 30 [30] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Total OCA at Week 30 [31] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 30. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 30
|
||||||||||||||||
Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [32] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Total OCA at Week 30 [33] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [34] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Total OCA at Week 48 [35] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [36] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Total OCA at Week 48 [37] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [38] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Total OCA at Week 48 [39] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 48. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 48
|
||||||||||||||||
Notes [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [40] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Total OCA at Week 48 [41] | ||||||||||||||||
End point description |
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [42] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Unconjugated OCA at Week 12 [43] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [44] - No participant started OCA 5 mg twice weekly at Week 12. [45] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Unconjugated OCA at Week 12 [46] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [47] - No participant started OCA 5 mg twice weekly at Week 12. [48] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Unconjugated OCA at Week 12 [49] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 12.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 12
|
||||||||||||||||
Notes [49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [50] - No participant started OCA 5 mg twice weekly at Week 12. [51] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Unconjugated OCA at Week 12 [52] | ||||||||||||||||
End point description |
AUC0-24 was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [53] - No participant started OCA 5 mg twice weekly at Week 12. [54] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Unconjugated OCA at Week 18 [55] | ||||||||||||||||
End point description |
Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [55] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [56] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Unconjugated OCA at Week 18 [57] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [57] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [58] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Unconjugated OCA at Week 18 [59] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 18.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 18
|
||||||||||||||||
Notes [59] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [60] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Unconjugated OCA at Week 18 [61] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [61] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [62] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Unconjugated OCA at Week 24 [63] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [63] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [64] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Unconjugated OCA at Week 24 [65] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [65] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Unconjugated OCA at Week 24 [66] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 24.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 24
|
||||||||||||||||
Notes [66] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [67] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Unconjugated OCA at Week 24 [68] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [68] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [69] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Unconjugated OCA at Week 30 [70] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [70] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [71] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Unconjugated OCA at Week 30 [72] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [72] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Unconjugated OCA at Week 30 [73] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 30.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 30
|
||||||||||||||||
Notes [73] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [74] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Unconjugated OCA at Week 30 [75] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [75] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [76] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Unconjugated OCA at Week 48 [77] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [77] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [78] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Unconjugated OCA at Week 48 [79] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [79] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [80] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Unconjugated OCA at Week 48 [81] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 48.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 48
|
||||||||||||||||
Notes [81] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [82] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Unconjugated OCA at Week 48 [83] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [83] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [84] - No participant received OCA 5 mg once weekly at Week 48. [85] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Glyco-OCA at Week 12 [86] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [86] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [87] - No participant started OCA 5 mg twice weekly at Week 12. [88] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Glyco-OCA at Week 12 [89] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [89] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [90] - No participant started OCA 5 mg twice weekly at Week 12. [91] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Glyco-OCA at Week 12 [92] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 12.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 12
|
||||||||||||||||
Notes [92] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [93] - No participant started OCA 5 mg twice weekly at Week 12. [94] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Glyco-OCA at Week 12 [95] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [95] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [96] - No participant started OCA 5 mg twice weekly at Week 12. [97] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Metabolite to Parent Ratio of AUC-0-24h (MRAUC) of Glyco-OCA at Week 12 [98] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [98] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [99] - No participant started OCA 5 mg twice weekly at Week 12. [100] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Metabolite to Parent Ratio of Cmax (MRCmax) of Glyco-OCA at Week 12 [101] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [101] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [102] - No participant started OCA 5 mg twice weekly at Week 12. [103] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Glyco-OCA at Week 18 [104] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [104] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [105] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Glyco-OCA at Week 18 [106] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [106] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [107] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Glyco-OCA at Week 18 [108] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 18.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 18
|
||||||||||||||||
Notes [108] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [109] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Glyco-OCA at Week 18 [110] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [110] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [111] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Glyco-OCA at Week 18 [112] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [112] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [113] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Glyco-OCA at Week 18 [114] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [114] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [115] - No participant started OCA 10 mg twice weekly at Week 18. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Glyco-OCA at Week 24 [116] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [116] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [117] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Glyco-OCA at Week 24 [118] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [118] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Glyco-OCA at Week 24 [119] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 24.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 24
|
||||||||||||||||
Notes [119] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [120] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Glyco-OCA at Week 24 [121] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [121] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [122] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Glyco-OCA at Week 24 [123] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [123] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [124] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Glyco-OCA at Week 24 [125] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [125] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [126] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Glyco-OCA at Week 30 [127] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [127] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [128] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Glyco-OCA at Week 30 [129] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [129] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Glyco-OCA at Week 30 [130] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 30.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 30
|
||||||||||||||||
Notes [130] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [131] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Glyco-OCA at Week 30 [132] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [132] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [133] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Glyco-OCA at Week 30 [134] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [134] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [135] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Glyco-OCA at Week 30 [136] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [136] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [137] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Glyco-OCA at Week 48 [138] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [138] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [139] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Glyco-OCA at Week 48 [140] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [140] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [141] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Glyco-OCA at Week 48 [142] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 48.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 48
|
||||||||||||||||
Notes [142] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [143] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Glyco-OCA at Week 48 [144] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [144] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [145] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Glyco-OCA at Week 48 [146] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [146] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [147] - No participant received OCA 5 mg once weekly at Week 48. [148] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Glyco-OCA at Week 48 [149] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [149] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [150] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Tauro-OCA at Week 12 [151] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [151] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [152] - No participant started OCA 5 mg twice weekly at Week 12. [153] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Tauro-OCA at Week 12 [154] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [154] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [155] - No participant started OCA 5 mg twice weekly at Week 12. [156] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Tauro-OCA at Week 12 [157] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 12.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 12
|
||||||||||||||||
Notes [157] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [158] - No participant started OCA 5 mg twice weekly at Week 12. [159] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Tauro-OCA at Week 12 [160] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [160] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [161] - No participant started OCA 5 mg twice weekly at Week 12. [162] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Tauro-OCA at Week 12 [163] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [163] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [164] - No participant started OCA 5 mg twice weekly at Week 12. [165] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Tauro-OCA at Week 12 [166] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [166] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [167] - No participant started OCA 5 mg twice weekly at Week 12. [168] - No participant started OCA 10 mg twice weekly at Week 12. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Tauro-OCA at Week 18 [169] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [169] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [170] - No participant started OCA 10 mg twice weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Tauro-OCA at Week 18 [171] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [171] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [172] - No participant started OCA 10 mg twice weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Tauro-OCA at Week 18 [173] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 18.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 18
|
||||||||||||||||
Notes [173] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [174] - No participant started OCA 10 mg twice weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Tauro-OCA at Week 18 [175] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [175] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [176] - No participant started OCA 10 mg twice weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Tauro-OCA at Week 18 [177] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [177] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [178] - No participant started OCA 10 mg twice weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Tauro-OCA at Week 18 [179] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.
Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [179] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [180] - No participant started OCA 10 mg twice weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Tauro-OCA at Week 24 [181] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [181] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [182] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Tauro-OCA at Week 24 [183] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [183] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Tauro-OCA at Week 24 [184] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 24.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 24
|
||||||||||||||||
Notes [184] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [185] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Tauro-OCA at Week 24 [186] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [186] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [187] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Tauro-OCA at Week 24 [188] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [188] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [189] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Tauro-OCA at Week 24 [190] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [190] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [191] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Tauro-OCA at Week 30 [192] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [192] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [193] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Tauro-OCA at Week 30 [194] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [194] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Tauro-OCA at Week 30 [195] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 30.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 30
|
||||||||||||||||
Notes [195] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [196] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Tauro-OCA at Week 30 [197] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [197] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [198] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Tauro-OCA at Week 30 [199] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [199] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [200] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Tauro-OCA at Week 30 [201] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [201] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [202] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of Tauro-OCA at Week 48 [203] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [203] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [204] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of Tauro-OCA at Week 48 [205] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [205] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [206] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of Tauro-OCA at Week 48 [207] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 48.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 48
|
||||||||||||||||
Notes [207] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [208] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of Tauro-OCA at Week 48 [209] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [209] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [210] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of Tauro-OCA at Week 48 [211] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [211] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [212] - No participant received OCA 5 mg once weekly at Week 48. [213] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of Tauro-OCA at Week 48 [214] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [214] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [215] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of OCA-glucuronide at Week 12 [216] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [216] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [217] - No participant started OCA 5 mg Twice Weekly at Week 12 [218] - No participant started OCA 10 mg Twice Weekly at Week 12 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of OCA-glucuronide at Week 12 [219] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. Pharmacokinetic of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [219] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [220] - No participant started OCA 5 mg Twice Weekly at Week 12 [221] - No participant started OCA 10 mg Twice Weekly at Week 12 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of OCA-glucuronide at Week 12 [222] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 12.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 12
|
||||||||||||||||
Notes [222] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [223] - No participant started OCA 5 mg Twice Weekly at Week 12 [224] - No participant started OCA 10 mg Twice Weekly at Week 12 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of OCA-glucuronide at Week 12 [225] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. Pharmacokinetic of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [225] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [226] - No participant started OCA 5 mg Twice Weekly at Week 12 [227] - No participant started OCA 10 mg Twice Weekly at Week 12 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of OCA-glucuronide at Week 12 [228] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [228] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [229] - No participant started OCA 5 mg Twice Weekly at Week 12 [230] - No participant started OCA 10 mg Twice Weekly at Week 12 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of OCA-glucuronide at Week 12 [231] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
|
||||||||||||||||
Notes [231] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [232] - No participant started OCA 5 mg Twice Weekly at Week 12 [233] - No participant started OCA 10 mg Twice Weekly at Week 12 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of OCA-glucuronide at Week 18 [234] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [234] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [235] - No participant started OCA 10 mg Twice Weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of OCA-glucuronide at Week 18 [236] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [236] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [237] - No participant started OCA 10 mg Twice Weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of OCA-glucuronide at Week 18 [238] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 18.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 18
|
||||||||||||||||
Notes [238] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [239] - No participant started OCA 10 mg Twice Weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of OCA-glucuronide at Week 18 [240] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [240] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [241] - No participant started OCA 10 mg Twice Weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of OCA-glucuronide at Week 18 [242] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [242] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [243] - No participant started OCA 10 mg Twice Weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of OCA-glucuronide at Week 18 [244] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.
Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
|
||||||||||||||||
Notes [244] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [245] - No participant started OCA 10 mg Twice Weekly at Week 18 |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of OCA-glucuronide at Week 24 [246] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [246] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [247] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of OCA-glucuronide at Week 24 [248] | ||||||||||||||||
End point description |
Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [248] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of OCA-glucuronide at Week 24 [249] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 24.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 24
|
||||||||||||||||
Notes [249] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [250] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of OCA-glucuronide at Week 24 [251] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [251] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [252] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of OCA-glucuronide at Week 24 [253] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [253] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [254] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of OCA-glucuronide at Week 24 [255] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
|
||||||||||||||||
Notes [255] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [256] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of OCA-glucuronide at Week 30 [257] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by dose regimen. Participants who received planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [257] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [258] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of OCA-glucuronide at Week 30 [259] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [259] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of OCA-glucuronide at Week 30 [260] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 30.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 30
|
||||||||||||||||
Notes [260] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [261] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of OCA-glucuronide at Week 30 [262] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [262] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [263] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of OCA-glucuronide at Week 30 [264] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [264] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [265] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of OCA-glucuronide at Week 30 [266] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
|
||||||||||||||||
Notes [266] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [267] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Cmax of OCA-glucuronide at Week 48 [268] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [268] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [269] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Tmax of OCA-glucuronide at Week 48 [270] | ||||||||||||||||
End point description |
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [270] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [271] - No participant OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Ctrough of OCA-glucuronide at Week 48 [272] | ||||||||||||||||
End point description |
Ctrough was considered as the concentration at 24-hours post-dose at Week 48.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
24 hours post-dose at Week 48
|
||||||||||||||||
Notes [272] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [273] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC0-24h of OCA-glucuronide at Week 48 [274] | ||||||||||||||||
End point description |
AUC0-24h was calculated using the linear/linear trapezoidal rule.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [274] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [275] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRAUC of OCA-glucuronide at Week 48 [276] | ||||||||||||||||
End point description |
MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [276] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [277] - No participant received OCA 5 mg once weekly at Week 48. [278] - 99999: Standard deviation is not estimable as there is only one participant. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
MRCmax of OCA-glucuronide at Week 48 [279] | ||||||||||||||||
End point description |
MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.
APD: Results of PK were planned to be listed by the dose regimen. Participants in the PK population who received the planned dose regimen and had available data were included in the analysis. PK of OCA 5 mg once weekly at Week 48 is not applicable as participants received either OCA 5 mg twice daily or 10 mg twice daily and no participant received OCA 5 mg once weekly at Week 48.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
|
||||||||||||||||
Notes [279] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
Notes [280] - No participant received OCA 5 mg once weekly at Week 48. |
|||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [281] | |||||||||||||||
End point description |
An adverse event (AE) was any unfavorable & unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study drug, whether or not related to study drug. An SAE was any AE that resulted in death, was life-threatening, resulted in a persistent or significant disability/incapacity, resulted in in-patient hospitalization or prolonged an existing hospitalization, was a congenital anomaly/birth defect, or was an important medical event that could jeopardize participant or could have required medical intervention to prevent one of the outcomes listed above. TEAE was defined as any AE if it met one or more of the following criteria: 1)An AE started on or after first study drug dose & within 30 days after last dose of study drug, 2)An AE occurred prior to first study drug dose that worsens after the first study drug dose.
APD: Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo)
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
Baseline up to approximately 3 years
|
|||||||||||||||
Notes [281] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, statistical analysis was not planned for this endpoint. |
||||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The MELD scoring system is used to assess the severity of chronic liver disease. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and prothrombin international normalized ratio (INR): 3.78× log normal (ln) [total bilirubin (mg/deciliter [dL])] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
APD: Intent-to-treat (ITT) population included all randomized participants who received any amount of investigational product (OCA or placebo). Participants with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [282] - 99999 denotes data not available as there were no participants at specified timepoint. [283] - 99999 denotes data not available as there were no participants at specified timepoint. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The MELD-Na scoring system is used to assess the severity of chronic liver disease in the participants with an initial MELD(i) score greater than 11. MELD-Na score is derived from the participant's serum total bilirubin, serum creatinine, INR, and sodium. The MELD-Na score is re-calculated as follows: MELD-Na = MELD(i) + 1.32*(137-Na) – [0.033*MELD(i)*(137-Na)]. MELD score ranges from 6-40 with higher scores indicating more severe liver disease and a worse outcome.
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [284] - 99999 denotes data not available as there were no participants. [285] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15 | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The Child-Pugh classification was a scoring system used for the classification of the severity of cirrhosis. It included three continuous variables (bilirubin, albumin, and INR) and two discrete variables (ascites and encephalopathy). Each variable was scored 1-3 with 3 indicating most severe derangement. The determination of child-pugh score ranged from 5 to 15. The higher the score, the sicker the participant.
APD: Participants in the ITT population with available data were analyzed.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [286] - 99999 denotes data not available as there were no participants. [287] - 99999 denotes data not available as there were no participants. |
||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants by Child-Pugh Score Component (Ascites Categories) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of participants with Child-Pugh component - ascites categories of none, mild, and moderate-severe has been reported. The ascites categories were defined per investigator’s discretion.
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants by Child-Pugh Score Component (Prothrombin Time Categories) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of participants with Child-Pugh component - prothrombin time (measured as INR) in categories of <1.7, 1.7 - 2.3, and >2.3 has been reported.
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants by Child-Pugh Score Component (Serum Albumin Categories) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of participants with Child-Pugh component - serum albumin levels in categories of >35 gram per liter (g/L), 28-35 g/L, or <28 g/L has been reported.
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants by Child-Pugh Score Component (Total Bilirubin Categories) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of participants with Child-Pugh component - total bilirubin levels in categories of <34 micromole per liter (μmol/ L), 34-50 μmol/L, and >50 μmol/L has been reported.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants by Child-Pugh Score Component (Hepatic Encephalopathy Categories) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of participants with Child-Pugh component - Hepatic encephalopathy in categories of Grade 0, Grade 1 or 2, and Grade 3 and 4 has been reported.
Grade 0: normal consciousness, normal personality, normal neurological examination, normal electroencephalogram.
Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles, per second (cps) waves.
Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves.
Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves.
Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cps delta activity.
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Total Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [288] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [289] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [290] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [291] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [292] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [293] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [294] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [295] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [296] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Platelets at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [297] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3 | ||||||||||||||||||||||||||||||||||||
End point description |
Total bile acids (micromole [μM]) = total ursodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total cholic acid (unconjugated, glyco-conjugate, tauroconjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM.
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 6, 12, 18, 24, 30, 36, 48; and Extension Month 3
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [298] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3 | ||||||||||||||||||||||||||||||||||||
End point description |
Total endogenous bile acids (μM) = total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total cholic acid (unconjugated, glycoconjugate, tauro-conjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM.
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [299] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in 7α-hydroxy-4-cholesten-3-one (C4) at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3 | ||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [300] - 99999 denotes data not available as there were no participants. |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3 | ||||||||||||||||||||||||||||||||||||
End point description |
APD: Participants in the ITT population with available data were analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to approximately 3 years
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo).
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Obeticholic Acid (OCA)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants initiated treatment with OCA 5 mg tablets orally once weekly. At Week 12, if there were no safety concerns, the dose was up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose was considered. At each titration visit, the participants started the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration was OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration was 48 Weeks. Participants, who had completed their 48 Week treatment, could continue the treatment until all randomized participants had completed their 48 Week treatment period and the database for that period was locked (total duration: approximately up to 3 years). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received OCA matching placebo tablets orally once weekly or twice weekly for the duration of at least 48 Weeks. Participants, who had completed their 48 Week treatment, could continue the treatment until all randomized participants had completed their 48 Week treatment period and the database for that period was locked (total duration: approximately up to 3 years). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
22 May 2017 |
The changes in Version 2 were incorporated based on Food and Drug Administration (FDA) review of Version 1 of the protocol:
• Background information was included to estimate the exposure difference between healthy subjects and subjects with moderate hepatic impairment to support the rationale for dose selection
• Additional PK sampling times were added to adequately characterize the PK of OCA and its active metabolites at steady state in subjects with moderate and severe impairment when dosing weekly to biweekly
• The period between screening and Day 1 was extended to at least 14 days to establish a baseline for serum biomarkers with at least two samples two weeks apart
• The Week 3 contact Visit by email/telephone was changed to a Safety Visit to assess evidence of early hepatotoxicity
• Guidelines were added to assess subjects for evidence of hepatotoxicity at each visit |
||
04 Jan 2018 |
• The Introduction was revised to highlight the need for close monitoring specifically in subjects with clinical evidence of hepatic decompensation and other complications due to advanced cirrhosis.
• Dosing regimens were updated to modify dosing to one regimen for subjects with moderate and severe hepatic impairment [e.g., same for child-pugh B and child-pugh C ], not to exceed 10 mg twice weekly, to align with label dosing guidelines. Titration was then only based on tolerability and not CP score.
• Reference to an option for open-label treatment was removed. An open-label extension was to be considered only after review of blinded safety and PK data from the double-blind treatment period.
• Protocol was updated with discontinuation criteria for decompensation events and biochemical thresholds. A plan for monitoring and drug-induced liver injury algorithm was included to ensure careful monitoring and drug interruption/discontinuation. Analysis of decompensation events as adverse events of interest was added. Additionally, “Close Observation” per FDA Guidance for Industry on Drug Induced Liver Injury (DILI) was clearly defined in the protocol to ensure that subjects who experienced a potential DILI underwent a full evaluation.
• Guidance was added that subjects should have been instructed to contact the site promptly upon awareness if they developed signs and symptoms of potential hepatic decompensation.
• Guidance was added that the Investigator should have contacted the study Medical Monitor upon awareness when any signs and symptoms of hepatic decompensation were observed in any subject.
• Guidance was added for monitoring amylase and lipase levels in subjects with suspected acute pancreatitis.
• Gallbladder assessments were added at Screening or Day 1. |
||
15 Feb 2019 |
• Updated clinical development data based on IB Version 18 (31 Jan 2019).
• Exclusion criteria were updated to mitigate the inclusion of subjects who may have been pregnant or breastfeeding as an additional safety precaution or who had a known history of human immunodeficiency syndrome infection.
• Exclusion criteria and prohibited medications sections were updated to prevent the concomitant use of fibrates and OCA. The primary objective of this study was to characterize the PK of OCA in subjects with PBC and mild to severe hepatic impairment. The drug-drug interactions of OCA with fibrates were not yet fully characterized in any population and were being restricted in this study as an additional safety precaution until data were available in a less advanced population. |
||
19 May 2020 |
• Addendum was issued to multiple countries to describe the requirements and processes under which subjects who were unable to return to study sites during the COVID-19 pandemic may have completed protocol specified assessments and continued to receive investigational product until in-person site visits could resume. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |