Trial Outcomes & Findings for Study of Obeticholic Acid (OCA) Evaluating Pharmacokinetics and Safety in Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment (NCT NCT03633227)
NCT ID: NCT03633227
Last Updated: 2022-09-06
Results Overview
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
22 participants
Primary outcome 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
Results posted on
2022-09-06
Participant Flow
This study was conducted at study sites in the United States, Argentina, Belgium, Spain, Lithuania, Brazil, Australia, Germany, Estonia, Italy, Hungary, and Canada.
A total of 31 participants were screened and 22 participants were randomized.
Participant milestones
| Measure |
Placebo
Participants received obeticholic acid (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).
|
Obeticholic Acid (OCA)
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. 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).
|
|---|---|---|
|
Double Blind (DB), up to Week 48
STARTED
|
12
|
10
|
|
Double Blind (DB), up to Week 48
COMPLETED
|
4
|
6
|
|
Double Blind (DB), up to Week 48
NOT COMPLETED
|
8
|
4
|
|
DB Extension, Week 48 up to 3 Years
STARTED
|
4
|
6
|
|
DB Extension, Week 48 up to 3 Years
COMPLETED
|
0
|
0
|
|
DB Extension, Week 48 up to 3 Years
NOT COMPLETED
|
4
|
6
|
Reasons for withdrawal
| Measure |
Placebo
Participants received obeticholic acid (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).
|
Obeticholic Acid (OCA)
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. 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).
|
|---|---|---|
|
Double Blind (DB), up to Week 48
Withdrawal by Subject
|
1
|
1
|
|
Double Blind (DB), up to Week 48
Death
|
2
|
1
|
|
Double Blind (DB), up to Week 48
Adverse Event
|
0
|
1
|
|
Double Blind (DB), up to Week 48
Study Terminated by Sponsor
|
2
|
1
|
|
Double Blind (DB), up to Week 48
Physician Decision
|
1
|
0
|
|
Double Blind (DB), up to Week 48
Liver Transplant During the Course of the Study
|
1
|
0
|
|
Double Blind (DB), up to Week 48
Multiple Serious Adverse Events and Drug Interruptions
|
1
|
0
|
|
DB Extension, Week 48 up to 3 Years
Withdrawal by Subject
|
0
|
2
|
|
DB Extension, Week 48 up to 3 Years
Death
|
0
|
1
|
|
DB Extension, Week 48 up to 3 Years
Study Terminated by Sponsor
|
3
|
2
|
|
DB Extension, Week 48 up to 3 Years
Lost to Follow-up
|
1
|
0
|
|
DB Extension, Week 48 up to 3 Years
Physician Decision
|
0
|
1
|
Baseline Characteristics
Study of Obeticholic Acid (OCA) Evaluating Pharmacokinetics and Safety in Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment
Baseline characteristics by cohort
| Measure |
Placebo
n=12 Participants
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).
|
Obeticholic Acid (OCA)
n=10 Participants
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).
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.5 years
STANDARD_DEVIATION 9.10 • n=39 Participants
|
60.5 years
STANDARD_DEVIATION 10.19 • n=41 Participants
|
61.6 years
STANDARD_DEVIATION 9.43 • n=35 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
16 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
10 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
12 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=39 Participants
|
10 Participants
n=41 Participants
|
21 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
PRIMARY outcome
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 12Population: 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 in the analysis. No participant started OCA 5 mg twice weekly or 10 mg twice weekly at Week 12.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. Pharmacokinetics (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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of Total OCA at Week 12
|
293 nanogram per milliliter (ng/mL)
Standard Deviation 189
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of Total OCA at Week 12
|
2.02 hours
Interval 2.0 to 3.0
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 12Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Trough Concentration (Ctrough) of Total OCA at Week 12
|
77.6 ng/mL
Standard Deviation 49.7
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Area Under the Concentration Versus Time Curve From Zero Time to 24 Hours (AUC0-24h) of Total OCA at Week 12
|
2970 nanogram*hour per milliliter (ng*h/mL)
Standard Deviation 1650
|
—
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Total OCA at Week 18
|
136 ng/mL
Standard Deviation 77.6
|
406 ng/mL
Standard Deviation 120
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Total OCA at Week 18
|
0.750 hours
Interval 0.5 to 1.0
|
2.52 hours
Interval 2.0 to 3.03
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Total OCA at Week 18
|
28.7 ng/mL
Standard Deviation 13.6
|
187 ng/mL
Standard Deviation 147
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Total OCA at Week 18
|
1380 ng*h/mL
Standard Deviation 776
|
5810 ng*h/mL
Standard Deviation 3600
|
—
|
PRIMARY outcome
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 24Population: 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Total OCA at Week 24
|
263 ng/mL
Standard Deviation 261
|
195 ng/mL
|
622 ng/mL
Standard Deviation 117
|
PRIMARY outcome
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 24Population: 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Total OCA at Week 24
|
5.04 hours
Interval 4.0 to 6.08
|
0.750 hours
Interval 0.75 to 0.75
|
2.27 hours
Interval 2.0 to 2.53
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 24Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Total OCA at Week 24
|
132 ng/mL
Standard Deviation 163
|
41.4 ng/mL
|
435 ng/mL
Standard Deviation 28.6
|
PRIMARY outcome
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 24Population: 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Total OCA at Week 24
|
4500 ng*h/mL
Standard Deviation 4910
|
2020 ng*h/mL
|
11300 ng*h/mL
Standard Deviation 2950
|
PRIMARY outcome
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 30Population: 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Total OCA at Week 30
|
125 ng/mL
|
277 ng/mL
Standard Deviation 64.7
|
674 ng/mL
Standard Deviation 310
|
PRIMARY outcome
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 30Population: 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Total OCA at Week 30
|
1.00 hours
Interval 1.0 to 1.0
|
4.52 hours
Interval 4.03 to 5.0
|
3.77 hours
Interval 2.53 to 5.0
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 30Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Total OCA at Week 30
|
22.3 ng/mL
|
217 ng/mL
Standard Deviation 15.7
|
317 ng/mL
Standard Deviation 248
|
PRIMARY outcome
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 30Population: 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Total OCA at Week 30
|
1260 ng*h/mL
|
5040 ng*h/mL
Standard Deviation 855
|
10500 ng*h/mL
Standard Deviation 7000
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Total OCA at Week 48
|
—
|
200 ng/mL
Standard Deviation 15.1
|
728 ng/mL
Standard Deviation 27.5
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Total OCA at Week 48
|
—
|
1.73 hours
Interval 1.47 to 2.0
|
4.03 hours
Interval 2.0 to 6.05
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 48Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Total OCA at Week 48
|
—
|
88.3 ng/mL
Standard Deviation 29.9
|
497 ng/mL
Standard Deviation 135
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Total OCA at Week 48
|
—
|
3210 ng*h/mL
Standard Deviation 56.7
|
13900 ng*h/mL
Standard Deviation 452
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Unconjugated OCA at Week 12
|
107 ng/mL
Standard Deviation 62.0
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Unconjugated OCA at Week 12
|
1.43 hours
Interval 1.0 to 1.5
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 12Population: 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. Pharmacokinetics 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 12.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Unconjugated OCA at Week 12
|
2.92 ng/mL
Standard Deviation 2.51
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
AUC0-24 was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=3 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Unconjugated OCA at Week 12
|
278 ng*h/mL
Standard Deviation 142
|
—
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Unconjugated OCA at Week 18
|
107 ng/mL
Standard Deviation 47.4
|
109 ng/mL
Standard Deviation 90.3
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Unconjugated OCA at Week 18
|
0.750 hours
Interval 0.5 to 1.0
|
1.24 hours
Interval 1.0 to 1.48
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Ctrough was considered as the concentration at 24-hours post-dose at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Unconjugated OCA at Week 18
|
3.38 ng/mL
Standard Deviation 0.262
|
3.56 ng/mL
Standard Deviation 4.01
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Unconjugated OCA at Week 18
|
191 ng*h/mL
Standard Deviation 125
|
263 ng*h/mL
Standard Deviation 247
|
—
|
PRIMARY outcome
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 24Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Unconjugated OCA at Week 24
|
115 ng/mL
Standard Deviation 98.2
|
157 ng/mL
|
168 ng/mL
Standard Deviation 92.6
|
PRIMARY outcome
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 24Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Unconjugated OCA at Week 24
|
1.13 hours
Interval 0.75 to 1.5
|
0.500 hours
Interval 0.5 to 0.5
|
1.63 hours
Interval 1.58 to 1.67
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 24Population: 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 24.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Unconjugated OCA at Week 24
|
2.46 ng/mL
Standard Deviation 2.05
|
5.18 ng/mL
|
8.77 ng/mL
Standard Deviation 11.4
|
PRIMARY outcome
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 24Population: 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Unconjugated OCA at Week 24
|
235 ng*h/mL
Standard Deviation 130
|
345 ng*h/mL
|
480 ng*h/mL
Standard Deviation 414
|
PRIMARY outcome
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 30Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Unconjugated OCA at Week 30
|
92.6 ng/mL
|
132 ng/mL
Standard Deviation 24.0
|
115 ng/mL
Standard Deviation 40.9
|
PRIMARY outcome
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 30Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Unconjugated OCA at Week 30
|
0.750 hours
Interval 0.75 to 0.75
|
1.17 hours
Interval 1.0 to 1.33
|
1.75 hours
Interval 0.5 to 3.0
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 30Population: 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 30.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Unconjugated OCA at Week 30
|
3.03 ng/mL
|
4.27 ng/mL
Standard Deviation 4.85
|
3.20 ng/mL
Standard Deviation 3.14
|
PRIMARY outcome
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 30Population: 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Unconjugated OCA at Week 30
|
176 ng*h/mL
|
304 ng*h/mL
Standard Deviation 82.3
|
473 ng*h/mL
Standard Deviation 397
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Unconjugated OCA at Week 48
|
—
|
131 ng/mL
Standard Deviation 31.8
|
284 ng/mL
Standard Deviation 177
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Unconjugated OCA at Week 48
|
—
|
1.10 hours
Interval 0.7 to 1.5
|
0.500 hours
Interval 0.5 to 0.5
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 48Population: 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. Pharmacokinetics 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 48.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Unconjugated OCA at Week 48
|
—
|
3.43 ng/mL
Standard Deviation 3.90
|
4.72 ng/mL
Standard Deviation 6.67
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=1 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Unconjugated OCA at Week 48
|
—
|
376 ng*h/mL
Standard Deviation 118
|
1190 ng*h/mL
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Glyco Conjugate of OCA (Glyco-OCA) at Week 12
|
117 ng/mL
Standard Deviation 55.0
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Glyco-OCA at Week 12
|
5.00 hours
Interval 3.92 to 5.0
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 12Population: 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. Pharmacokinetics 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 12.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Glyco-OCA at Week 12
|
47.1 ng/mL
Standard Deviation 31.1
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Glyco-OCA at Week 12
|
1690 ng*h/mL
Standard Deviation 947
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=3 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Metabolite to Parent Ratio of AUC-0-24h (MRAUC) of Glyco-OCA at Week 12
|
4.36 ratio
Standard Deviation 1.03
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Metabolite to Parent Ratio of Cmax (MRCmax) of Glyco-OCA at Week 12
|
1.39 ratio
Standard Deviation 1.38
|
—
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Glyco-OCA at Week 18
|
52.7 ng/mL
Standard Deviation 4.31
|
213 ng/mL
Standard Deviation 22.6
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Glyco-OCA at Week 18
|
4.25 hours
Interval 2.5 to 6.0
|
2.52 hours
Interval 2.0 to 3.03
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Ctrough was considered as the concentration at 24-hours post-dose at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Glyco-OCA at Week 18
|
13.3 ng/mL
Standard Deviation 5.03
|
98.1 ng/mL
Standard Deviation 53.7
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Glyco-OCA at Week 18
|
625 ng*h/mL
Standard Deviation 147
|
3020 ng*h/mL
Standard Deviation 1120
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Glyco-OCA at Week 18
|
3.39 ratio
Standard Deviation 1.55
|
21.2 ratio
Standard Deviation 23.6
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Glyco-OCA at Week 18
|
0.487 ratio
Standard Deviation 0.250
|
2.73 ratio
Standard Deviation 2.44
|
—
|
PRIMARY outcome
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 24Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Glyco-OCA at Week 24
|
166 ng/mL
Standard Deviation 163
|
56.2 ng/mL
|
294 ng/mL
Standard Deviation 70.0
|
PRIMARY outcome
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 24Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Glyco-OCA at Week 24
|
5.04 hours
Interval 4.0 to 6.08
|
5.00 hours
Interval 5.0 to 5.0
|
4.54 hours
Interval 4.08 to 5.0
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 24Population: 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 24.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Glyco-OCA at Week 24
|
83.0 ng/mL
Standard Deviation 106
|
22.0 ng/mL
|
239 ng/mL
Standard Deviation 7.07
|
PRIMARY outcome
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 24Population: 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Glyco-OCA at Week 24
|
2710 ng*h/mL
Standard Deviation 3030
|
936 ng*h/mL
|
5550 ng*h/mL
Standard Deviation 878
|
PRIMARY outcome
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 24Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Glyco-OCA at Week 24
|
8.26 ratio
Standard Deviation 6.80
|
2.39 ratio
|
17.3 ratio
Standard Deviation 16.5
|
PRIMARY outcome
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 24Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Glyco-OCA at Week 24
|
1.17 ratio
Standard Deviation 0.253
|
0.315 ratio
|
1.94 ratio
Standard Deviation 1.44
|
PRIMARY outcome
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 30Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Glyco-OCA at Week 30
|
83.0 ng/mL
|
174 ng/mL
Standard Deviation 75.0
|
301 ng/mL
Standard Deviation 86.3
|
PRIMARY outcome
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 30Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Glyco-OCA at Week 30
|
6.00 hours
Interval 6.0 to 6.0
|
14.0 hours
Interval 4.03 to 24.0
|
4.51 hours
Interval 4.02 to 5.0
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 30Population: 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 30.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Glyco-OCA at Week 30
|
14.4 ng/mL
|
143 ng/mL
Standard Deviation 30.4
|
156 ng/mL
Standard Deviation 79.4
|
PRIMARY outcome
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 30Population: 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Glyco-OCA at Week 30
|
863 ng*h/mL
|
3180 ng*h/mL
Standard Deviation 1080
|
5050 ng*h/mL
Standard Deviation 2260
|
PRIMARY outcome
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 30Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Glyco-OCA at Week 30
|
4.31 ratio
|
10.0 ratio
Standard Deviation 5.84
|
17.2 ratio
Standard Deviation 18.7
|
PRIMARY outcome
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 30Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Glyco-OCA at Week 30
|
0.789 ratio
|
1.23 ratio
Standard Deviation 0.723
|
2.58 ratio
Standard Deviation 1.58
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Glyco-OCA at Week 48
|
—
|
123 ng/mL
Standard Deviation 34.0
|
354 ng/mL
Standard Deviation 37.5
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Glyco-OCA at Week 48
|
—
|
5.00 hours
Interval 5.0 to 5.0
|
4.03 hours
Interval 2.0 to 6.05
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 48Population: 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. Pharmacokinetics 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 48.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Glyco-OCA at Week 48
|
—
|
65.9 ng/mL
Standard Deviation 10.2
|
280 ng/mL
Standard Deviation 62.2
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Glyco-OCA at Week 48
|
—
|
2120 ng*h/mL
Standard Deviation 422
|
6950 ng*h/mL
Standard Deviation 648
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=1 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Glyco-OCA at Week 48
|
—
|
5.39 ratio
Standard Deviation 2.69
|
4.79 ratio
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Glyco-OCA at Week 48
|
—
|
0.826 ratio
Standard Deviation 0.0280
|
1.41 ratio
Standard Deviation 1.00
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Tauro Conjugate of OCA (Tauro-OCA) at Week 12
|
201 ng/mL
Standard Deviation 213
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Tauro-OCA at Week 12
|
5.00 hours
Interval 3.0 to 5.0
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 12Population: 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. Pharmacokinetics 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 12.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Tauro-OCA at Week 12
|
41.6 ng/mL
Standard Deviation 33.0
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Tauro-OCA at Week 12
|
1580 ng*h/mL
Standard Deviation 1260
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=3 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Tauro-OCA at Week 12
|
3.13 ratio
Standard Deviation 1.08
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Tauro-OCA at Week 12
|
2.24 ratio
Standard Deviation 2.46
|
—
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Tauro-OCA at Week 18
|
63.2 ng/mL
Standard Deviation 46.9
|
221 ng/mL
Standard Deviation 188
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Tauro-OCA at Week 18
|
5.00 hours
Interval 5.0 to 5.0
|
2.52 hours
Interval 2.0 to 3.03
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Ctrough was considered as the concentration at 24-hours post-dose at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Tauro-OCA at Week 18
|
17.0 ng/mL
Standard Deviation 11.2
|
122 ng/mL
Standard Deviation 130
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Tauro-OCA at Week 18
|
799 ng*h/mL
Standard Deviation 654
|
3630 ng*h/mL
Standard Deviation 3600
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Tauro-OCA at Week 18
|
3.11 ratio
Standard Deviation 0.685
|
28.8 ratio
Standard Deviation 37.9
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Tauro-OCA at Week 18
|
0.434 ratio
Standard Deviation 0.156
|
3.32 ratio
Standard Deviation 4.12
|
—
|
PRIMARY outcome
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 24Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Tauro-OCA at Week 24
|
142 ng/mL
Standard Deviation 144
|
65.5 ng/mL
|
430 ng/mL
Standard Deviation 142
|
PRIMARY outcome
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 24Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Tauro-OCA at Week 24
|
5.54 hours
Interval 5.0 to 6.08
|
9.00 hours
Interval 9.0 to 9.0
|
4.05 hours
Interval 3.1 to 5.0
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 24Population: 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 24.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Tauro-OCA at Week 24
|
71.0 ng/mL
Standard Deviation 90.5
|
21.2 ng/mL
|
271 ng/mL
Standard Deviation 58.0
|
PRIMARY outcome
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 24Population: 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Tauro-OCA at Week 24
|
2360 ng*h/mL
Standard Deviation 2650
|
1060 ng*h/mL
|
7470 ng*h/mL
Standard Deviation 3260
|
PRIMARY outcome
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 24Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Tauro-OCA at Week 24
|
6.51 ratio
Standard Deviation 5.40
|
2.46 ratio
|
23.4 ratio
Standard Deviation 25.6
|
PRIMARY outcome
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 24Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Tauro-OCA at Week 24
|
0.881 ratio
Standard Deviation 0.249
|
0.332 ratio
|
2.63 ratio
Standard Deviation 2.13
|
PRIMARY outcome
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 30Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Tauro-OCA at Week 30
|
38.6 ng/mL
|
141 ng/mL
Standard Deviation 13.4
|
460 ng/mL
Standard Deviation 342
|
PRIMARY outcome
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 30Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Tauro-OCA at Week 30
|
6.00 hours
Interval 6.0 to 6.0
|
4.52 hours
Interval 4.03 to 5.0
|
4.03 hours
Interval 3.05 to 5.0
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 30Population: 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 30.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Tauro-OCA at Week 30
|
8.21 ng/mL
|
110 ng/mL
Standard Deviation 7.78
|
222 ng/mL
Standard Deviation 228
|
PRIMARY outcome
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 30Population: 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Tauro-OCA at Week 30
|
408 ng*h/mL
|
2430 ng*h/mL
Standard Deviation 18.1
|
7020 ng*h/mL
Standard Deviation 6780
|
PRIMARY outcome
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 30Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Tauro-OCA at Week 30
|
1.84 ratio
|
6.61 ratio
Standard Deviation 1.74
|
25.7 ratio
Standard Deviation 33.0
|
PRIMARY outcome
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 30Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Tauro-OCA at Week 30
|
0.332 ratio
|
0.855 ratio
Standard Deviation 0.0746
|
3.85 ratio
Standard Deviation 3.73
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Tauro-OCA at Week 48
|
—
|
72.5 ng/mL
Standard Deviation 15.1
|
485 ng/mL
Standard Deviation 20.5
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of Tauro-OCA at Week 48
|
—
|
6.50 hours
Interval 6.0 to 7.0
|
2.57 hours
Interval 2.0 to 3.13
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 48Population: 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. Pharmacokinetics 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 48.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of Tauro-OCA at Week 48
|
—
|
33.7 ng/mL
Standard Deviation 21.4
|
309 ng/mL
Standard Deviation 109
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of Tauro-OCA at Week 48
|
—
|
1220 ng*h/mL
Standard Deviation 389
|
8890 ng*h/mL
Standard Deviation 696
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=1 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of Tauro-OCA at Week 48
|
—
|
2.59 ratio
Standard Deviation 0.00903
|
5.60 ratio
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of Tauro-OCA at Week 48
|
—
|
0.468 ratio
Standard Deviation 0.206
|
1.67 ratio
Standard Deviation 0.989
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of Glucuronide Metabolite of OCA (OCA-glucuronide) at Week 12
|
47.0 ng/mL
Standard Deviation 24.7
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of OCA-glucuronide at Week 12
|
2.50 hours
Interval 1.5 to 3.0
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 12Population: 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. Pharmacokinetics 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 12.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of OCA-glucuronide at Week 12
|
20.7 ng/mL
Standard Deviation 15.4
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=4 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of OCA-glucuronide at Week 12
|
593 ng*h/mL
Standard Deviation 388
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=3 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of OCA-glucuronide at Week 12
|
1.17 ratio
Standard Deviation 0.638
|
—
|
—
|
PRIMARY outcome
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 12Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=5 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of OCA-glucuronide at Week 12
|
0.384 ratio
Standard Deviation 0.275
|
—
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of OCA-glucuronide at Week 18
|
39.2 ng/mL
Standard Deviation 30.3
|
74.9 ng/mL
Standard Deviation 38.4
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of OCA-glucuronide at Week 18
|
1.25 hours
Interval 1.0 to 1.5
|
2.73 hours
Interval 1.5 to 3.97
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
Ctrough was considered as the concentration at 24-hours post-dose at Week 18.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of OCA-glucuronide at Week 18
|
11.7 ng/mL
Standard Deviation 7.55
|
40.9 ng/mL
Standard Deviation 43.9
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of OCA-glucuronide at Week 18
|
390 ng*h/mL
Standard Deviation 278
|
1120 ng*h/mL
Standard Deviation 989
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of OCA-glucuronide at Week 18
|
1.41 ratio
Standard Deviation 0.101
|
7.58 ratio
Standard Deviation 9.76
|
—
|
PRIMARY outcome
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 18Population: 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. Pharmacokinetics of OCA 10 mg twice weekly at Week 18 is not applicable as no participant started 10 mg twice weekly at Week 18.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of OCA-glucuronide at Week 18
|
0.236 ratio
Standard Deviation 0.0942
|
0.891 ratio
Standard Deviation 0.985
|
—
|
PRIMARY outcome
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 24Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of OCA-glucuronide at Week 24
|
20.2 ng/mL
Standard Deviation 7.42
|
58.1 ng/mL
|
127 ng/mL
Standard Deviation 71.0
|
PRIMARY outcome
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 24Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of OCA-glucuronide at Week 24
|
2.54 hours
Interval 2.08 to 3.0
|
1.00 hours
Interval 1.0 to 1.0
|
2.27 hours
Interval 2.0 to 2.53
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 24Population: 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 24.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of OCA-glucuronide at Week 24
|
11.6 ng/mL
Standard Deviation 6.43
|
14.5 ng/mL
|
84.2 ng/mL
Standard Deviation 81.7
|
PRIMARY outcome
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 24Population: 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of OCA-glucuronide at Week 24
|
330 ng*h/mL
Standard Deviation 191
|
602 ng*h/mL
|
2120 ng*h/mL
Standard Deviation 1920
|
PRIMARY outcome
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 24Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of OCA-glucuronide at Week 24
|
0.983 ratio
Standard Deviation 0.0286
|
1.23 ratio
|
6.87 ratio
Standard Deviation 8.74
|
PRIMARY outcome
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 24Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of OCA-glucuronide at Week 24
|
0.165 ratio
Standard Deviation 0.0959
|
0.261 ratio
|
0.727 ratio
Standard Deviation 0.701
|
PRIMARY outcome
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 30Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of OCA-glucuronide at Week 30
|
13.7 ng/mL
|
51.9 ng/mL
Standard Deviation 49.4
|
148 ng/mL
Standard Deviation 117
|
PRIMARY outcome
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 30Population: 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of OCA-glucuronide at Week 30
|
1.50 hours
Interval 1.5 to 1.5
|
2.26 hours
Interval 1.5 to 3.02
|
4.51 hours
Interval 4.02 to 5.0
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 30Population: 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 30.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of OCA-glucuronide at Week 30
|
5.57 ng/mL
|
19.7 ng/mL
Standard Deviation 13.8
|
89.0 ng/mL
Standard Deviation 107
|
PRIMARY outcome
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 30Population: 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of OCA-glucuronide at Week 30
|
170 ng*h/mL
|
641 ng*h/mL
Standard Deviation 482
|
2200 ng*h/mL
Standard Deviation 2100
|
PRIMARY outcome
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 30Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of OCA-glucuronide at Week 30
|
0.680 ratio
|
1.39 ratio
Standard Deviation 0.742
|
7.10 ratio
Standard Deviation 9.09
|
PRIMARY outcome
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 30Population: 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=1 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of OCA-glucuronide at Week 30
|
0.104 ratio
|
0.257 ratio
Standard Deviation 0.217
|
1.11 ratio
Standard Deviation 1.11
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Cmax of OCA-glucuronide at Week 48
|
—
|
66.0 ng/mL
Standard Deviation 63.6
|
134 ng/mL
Standard Deviation 71.3
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Tmax of OCA-glucuronide at Week 48
|
—
|
1.73 hours
Interval 1.47 to 2.0
|
1.54 hours
Interval 1.5 to 1.58
|
PRIMARY outcome
Timeframe: 24 hours post-dose at Week 48Population: 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. Pharmacokinetics 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.
Ctrough was considered as the concentration at 24-hours post-dose at Week 48.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Ctrough of OCA-glucuronide at Week 48
|
—
|
39.2 ng/mL
Standard Deviation 35.7
|
89.2 ng/mL
Standard Deviation 73.3
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
AUC0-24h was calculated using the linear/linear trapezoidal rule.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
AUC0-24h of OCA-glucuronide at Week 48
|
—
|
952 ng*h/mL
Standard Deviation 833
|
2490 ng*h/mL
Standard Deviation 1520
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=1 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRAUC of OCA-glucuronide at Week 48
|
—
|
1.62 ratio
Standard Deviation 1.05
|
0.833 ratio
|
PRIMARY outcome
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 48Population: 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. Pharmacokinetics 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.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=2 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
n=2 Participants
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
MRCmax of OCA-glucuronide at Week 48
|
—
|
0.411 ratio
Standard Deviation 0.444
|
0.482 ratio
Standard Deviation 0.479
|
PRIMARY outcome
Timeframe: Baseline up to approximately 3 yearsPopulation: The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug. An SAE was any AE that results 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 the 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 the first study drug dose and within 30 days after the last dose of study drug, 2) An AE occurred prior to the first study drug dose that worsens (increase in grade) after the first study drug dose.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Any TEAE
|
12 Participants
|
10 Participants
|
—
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAE
|
9 Participants
|
7 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 36
|
0.15 score on a scale
Interval -1.0 to 1.5
|
0.25 score on a scale
Interval -1.5 to 1.0
|
—
|
|
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
0.65 score on a scale
Interval 0.0 to 1.5
|
-1.75 score on a scale
Interval -2.5 to -0.5
|
—
|
|
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
Change at Extension Month 3
|
0.50 score on a scale
Interval 0.5 to 4.3
|
-1.00 score on a scale
Interval -1.5 to -0.5
|
—
|
|
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
Change at Extension Month 6
|
0.00 score on a scale
Interval -1.0 to 3.5
|
0.25 score on a scale
Interval 0.0 to 0.5
|
—
|
|
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
Change at Extension Month 9
|
—
|
0.75 score on a scale
Interval -1.0 to 2.5
|
—
|
|
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
Change at Extension Month 12
|
-1.00 score on a scale
Interval -1.0 to -1.0
|
4.50 score on a scale
Interval 4.5 to 4.5
|
—
|
|
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
Change at Extension Month 15
|
-1.00 score on a scale
Interval -1.0 to -1.0
|
—
|
—
|
|
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Baseline
|
11.75 score on a scale
Interval 10.6 to 13.5
|
12.75 score on a scale
Interval 9.5 to 16.0
|
—
|
|
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 3
|
0.50 score on a scale
Interval -0.5 to 1.0
|
0.00 score on a scale
Interval -1.5 to 2.0
|
—
|
|
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 6
|
0.50 score on a scale
Interval 0.0 to 2.5
|
0.00 score on a scale
Interval -0.75 to 1.25
|
—
|
|
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
Change at Week 12
|
0.75 score on a scale
Interval 0.0 to 2.5
|
0.00 score on a scale
Interval -1.0 to 1.0
|
—
|
|
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 18
|
0.65 score on a scale
Interval -0.25 to 3.0
|
-0.75 score on a scale
Interval -2.0 to 1.0
|
—
|
|
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 24
|
0.15 score on a scale
Interval 0.0 to 0.4
|
-1.50 score on a scale
Interval -2.0 to 0.0
|
—
|
|
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
0.15 score on a scale
Interval -0.5 to 0.5
|
-1.25 score on a scale
Interval -2.0 to 0.0
|
—
|
|
Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 42
|
0.65 score on a scale
Interval -0.5 to 1.5
|
0.50 score on a scale
Interval 0.0 to 1.5
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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. The MELD(i) 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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Baseline
|
11.75 score on a scale
Interval 10.6 to 14.25
|
13.25 score on a scale
Interval 9.5 to 16.0
|
—
|
|
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 3
|
0.00 score on a scale
Interval -0.5 to 1.0
|
0.50 score on a scale
Interval -1.5 to 2.0
|
—
|
|
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 6
|
0.50 score on a scale
Interval 0.0 to 2.0
|
-0.25 score on a scale
Interval -0.75 to 1.5
|
—
|
|
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
Change at Week 12
|
0.50 score on a scale
Interval 0.0 to 3.5
|
0.50 score on a scale
Interval -1.5 to 2.0
|
—
|
|
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 18
|
0.65 score on a scale
Interval -0.25 to 2.75
|
-0.75 score on a scale
Interval -2.5 to 0.5
|
—
|
|
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
Change at Week 24
|
0.15 score on a scale
Interval 0.0 to 0.4
|
-2.00 score on a scale
Interval -2.5 to 1.0
|
—
|
|
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
0.15 score on a scale
Interval -0.5 to 0.5
|
-0.75 score on a scale
Interval -2.0 to 0.5
|
—
|
|
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
Change at Week 36
|
0.15 score on a scale
Interval -1.0 to 1.5
|
-0.25 score on a scale
Interval -1.5 to 1.0
|
—
|
|
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 42
|
0.00 score on a scale
Interval -0.5 to 1.3
|
0.50 score on a scale
Interval 0.0 to 0.5
|
—
|
|
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
Change at Week 48
|
0.65 score on a scale
Interval 0.0 to 2.5
|
-1.75 score on a scale
Interval -3.0 to 0.0
|
—
|
|
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
2.50 score on a scale
Interval 0.5 to 4.3
|
-1.00 score on a scale
Interval -2.5 to -0.5
|
—
|
|
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
Change at Extension Month 6
|
0.00 score on a scale
Interval -1.0 to 3.5
|
1.75 score on a scale
Interval 0.5 to 3.0
|
—
|
|
Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 9
|
—
|
0.75 score on a scale
Interval -1.0 to 2.5
|
—
|
|
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
Change at Extension Month 12
|
-1.00 score on a scale
Interval -1.0 to -1.0
|
4.50 score on a scale
Interval 4.5 to 4.5
|
—
|
|
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
Change at Extension Month 15
|
-1.00 score on a scale
Interval -1.0 to -1.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 18
|
0.0 score on a scale
Interval -1.0 to 0.0
|
-0.5 score on a scale
Interval -2.0 to 0.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
-0.5 score on a scale
Interval -1.0 to 0.0
|
-1.0 score on a scale
Interval -2.0 to 0.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
-0.5 score on a scale
Interval -1.0 to 0.0
|
0.0 score on a scale
Interval -2.0 to 0.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
0.0 score on a scale
Interval -1.0 to 0.0
|
0.0 score on a scale
Interval -1.0 to 1.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Baseline
|
8.0 score on a scale
Interval 7.0 to 8.0
|
8.0 score on a scale
Interval 7.0 to 8.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Day 1
|
0.0 score on a scale
Interval -0.5 to 0.0
|
0.0 score on a scale
Interval 0.0 to 0.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 6
|
0.0 score on a scale
Interval -1.0 to 0.0
|
0.0 score on a scale
Interval -0.5 to 0.5
|
—
|
|
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
Change at Week 12
|
-0.5 score on a scale
Interval -1.0 to 1.0
|
0.0 score on a scale
Interval -1.0 to 1.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 24
|
-1.0 score on a scale
Interval -1.0 to 0.0
|
0.0 score on a scale
Interval -1.0 to 0.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 36
|
-1.0 score on a scale
Interval -1.0 to 0.0
|
-0.5 score on a scale
Interval -1.0 to 0.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 6
|
1.0 score on a scale
Interval -2.0 to 3.0
|
0.0 score on a scale
Interval 0.0 to 0.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 9
|
—
|
0.0 score on a scale
Interval -1.0 to 1.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 12
|
1.0 score on a scale
Interval 1.0 to 1.0
|
0.0 score on a scale
Interval 0.0 to 0.0
|
—
|
|
Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 15
|
1.0 score on a scale
Interval 1.0 to 1.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Baseline · None
|
6 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Baseline · Mild
|
5 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 9 · None
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 9 · Mild
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 9 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 12 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 15 · None
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 15 · Mild
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 15 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Day 1 · Moderate-Severe
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 6 · None
|
7 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 6 · Mild
|
2 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 6 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 12 · None
|
4 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 12 · Mild
|
2 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 12 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 18 · None
|
6 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 18 · Mild
|
2 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 18 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 24 · None
|
6 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 24 · Mild
|
0 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 24 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 30 · None
|
6 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 30 · Mild
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 30 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 36 · None
|
6 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 36 · Mild
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 36 · Moderate-Severe
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 48 · None
|
6 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 48 · Mild
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Week 48 · Moderate-Severe
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 3 · None
|
6 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 3 · Mild
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 3 · Moderate-Severe
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 6 · None
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 6 · Mild
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 6 · Moderate-Severe
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 12 · None
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Extension Month 12 · Mild
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Baseline · Moderate-Severe
|
1 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Day 1 · None
|
6 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
Day 1 · Mild
|
5 Participants
|
4 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Baseline · <1.7
|
12 Participants
|
10 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 12 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 12 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 24 · 1.7 - 2.3
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 24 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 30 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 36 · <1.7
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 36 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 48 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 48 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 15 · <1.7
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 15 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Baseline · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Baseline · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Day 1 · <1.7
|
12 Participants
|
10 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Day 1 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Day 1 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 6 · <1.7
|
9 Participants
|
9 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 6 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 6 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 12 · <1.7
|
6 Participants
|
7 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 18 · <1.7
|
8 Participants
|
8 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 18 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 18 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 24 · <1.7
|
4 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 30 · <1.7
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 30 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 36 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Week 48 · <1.7
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 3 · <1.7
|
6 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 3 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 3 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 6 · <1.7
|
3 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 6 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 6 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 9 · <1.7
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 9 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 9 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 12 · <1.7
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 12 · 1.7 - 2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 12 · >2.3
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
Extension Month 15 · >2.3
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 30 · 28 - 35 g/L
|
5 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 30 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 36 · >35 g/L
|
1 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 36 · 28 - 35 g/L
|
5 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 36 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 48 · >35 g/L
|
2 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 48 · 28 - 35 g/L
|
4 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 48 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Baseline · >35 g/L
|
3 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Baseline · 28 - 35 g/L
|
8 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Baseline · <28 g/L
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Day 1 · >35 g/L
|
3 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Day 1 · 28 - 35 g/L
|
9 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Day 1 · <28 g/L
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 12 · >35 g/L
|
1 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 12 · 28 - 35 g/L
|
5 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 12 · <28 g/L
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 6 · >35 g/L
|
2 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 6 · 28 - 35 g/L
|
7 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 6 · <28 g/L
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 18 · >35 g/L
|
2 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 18 · 28 - 35 g/L
|
6 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 18 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 24 · >35 g/L
|
1 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 24 · 28 - 35 g/L
|
5 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 24 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Week 30 · >35 g/L
|
1 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 3 · >35 g/L
|
1 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 3 · 28 - 35 g/L
|
5 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 3 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 6 · >35 g/L
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 6 · 28 - 35 g/L
|
2 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 6 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 9 · >35 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 9 · 28 - 35 g/L
|
0 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 9 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 12 · >35 g/L
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 12 · 28 - 35 g/L
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 12 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 15 · >35 g/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 15 · 28 - 35 g/L
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
Extension Month 15 · <28 g/L
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 18 · >50 µmol/L
|
3 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 24 · <34 µmol/L
|
2 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 9 · >50 µmol/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 12 · <34 µmol/L
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 15 · <34 µmol/L
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 48 · <34 µmol/L
|
2 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 48 · 34-50 µmol/L
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 48 · >50 µmol/L
|
3 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 3 · <34 µmol/L
|
2 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 3 · 34-50 µmol/L
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 3 · >50 µmol/L
|
3 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 6 · <34 µmol/L
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 6 · 34-50 µmol/L
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 6 · >50 µmol/L
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 9 · <34 µmol/L
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 9 · 34-50 µmol/L
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 12 · 34-50 µmol/L
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 12 · >50 µmol/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 15 · 34-50 µmol/L
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Extension Month 15 · >50 µmol/L
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Baseline · <34 µmol/L
|
3 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Baseline · 34-50 µmol/L
|
5 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Baseline · >50 µmol/L
|
4 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Day 1 · <34 µmol/L
|
3 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Day 1 · 34-50 µmol/L
|
5 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Day 1 · >50 µmol/L
|
4 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 6 · <34 µmol/L
|
4 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 6 · 34-50 µmol/L
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 6 · >50 µmol/L
|
4 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 12 · <34 µmol/L
|
2 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 12 · 34-50 µmol/L
|
3 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 12 · >50 µmol/L
|
1 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 18 · <34 µmol/L
|
2 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 18 · 34-50 µmol/L
|
3 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 24 · 34-50 µmol/L
|
3 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 24 · >50 µmol/L
|
1 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 30 · <34 µmol/L
|
3 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 30 · 34-50 µmol/L
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 30 · >50 µmol/L
|
2 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 36 · <34 µmol/L
|
3 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 36 · 34-50 µmol/L
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
Week 36 · >50 µmol/L
|
2 Participants
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Baseline · Grade 0
|
7 Participants
|
7 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Baseline · Grade 1 or 2
|
5 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Baseline · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Day 1 · Grade 0
|
8 Participants
|
8 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Day 1 · Grade 1 or 2
|
4 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Day 1 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 6 · Grade 0
|
6 Participants
|
6 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 6 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 12 · Grade 0
|
4 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 12 · Grade 1 or 2
|
2 Participants
|
2 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 12 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 18 · Grade 0
|
6 Participants
|
7 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 18 · Grade 1 or 2
|
2 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 18 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 24 · Grade 1 or 2
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 30 · Grade 1 or 2
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 30 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 36 · Grade 0
|
6 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 36 · Grade 1 or 2
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 36 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 48 · Grade 0
|
5 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 48 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 3 · Grade 0
|
5 Participants
|
4 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 3 · Grade 1 or 2
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 6 · Grade 0
|
3 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 6 · Grade 1 or 2
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 6 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 9 · Grade 0
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 9 · Grade 1 or 2
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 12 · Grade 0
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 12 · Grade 1 or 2
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 12 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 15 · Grade 1 or 2
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 6 · Grade 1 or 2
|
3 Participants
|
3 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 24 · Grade 0
|
6 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 24 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 30 · Grade 0
|
5 Participants
|
5 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Week 48 · Grade 1 or 2
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 3 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 9 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 15 · Grade 0
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
Extension Month 15 · Grade 3 or 4
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 3
|
0.86 μmol/L
Interval -13.0 to 6.5
|
-3.25 μmol/L
Interval -4.0 to 24.0
|
—
|
|
Change From Baseline in Total Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Baseline
|
45.38 μmol/L
Interval 34.57 to 55.79
|
41.50 μmol/L
Interval 19.0 to 106.88
|
—
|
|
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
Change at Week 6
|
3.00 μmol/L
Interval -1.5 to 5.99
|
-2.14 μmol/L
Interval -3.43 to 26.75
|
—
|
|
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
Change at Week 12
|
0.86 μmol/L
Interval -4.28 to 9.0
|
-1.71 μmol/L
Interval -6.0 to 17.96
|
—
|
|
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
Change at Week 18
|
1.08 μmol/L
Interval -4.7 to 16.05
|
-4.03 μmol/L
Interval -9.0 to 3.21
|
—
|
|
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
Change at Week 24
|
2.67 μmol/L
Interval -1.5 to 20.4
|
-3.50 μmol/L
Interval -10.0 to 1.71
|
—
|
|
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
Change at Week 30
|
2.08 μmol/L
Interval -2.57 to 31.34
|
-8.49 μmol/L
Interval -9.0 to -5.5
|
—
|
|
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
Change at Week 36
|
4.25 μmol/L
Interval -11.12 to 9.67
|
-3.53 μmol/L
Interval -7.0 to 3.42
|
—
|
|
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
Change at Week 42
|
6.58 μmol/L
Interval -7.7 to 12.0
|
1.71 μmol/L
Interval -2.85 to 6.0
|
—
|
|
Change From Baseline in Total Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
6.25 μmol/L
Interval -2.57 to 23.67
|
-3.75 μmol/L
Interval -6.27 to -0.57
|
—
|
|
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
Change at Extension Month 3
|
2.25 μmol/L
Interval 0.86 to 60.67
|
0.50 μmol/L
Interval -16.0 to 0.57
|
—
|
|
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
Change at Extension Month 6
|
-1.50 μmol/L
Interval -12.83 to 21.38
|
-0.22 μmol/L
Interval -1.0 to 0.57
|
—
|
|
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
Change at Extension Month 9
|
—
|
-7.86 μmol/L
Interval -18.0 to 2.28
|
—
|
|
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
Change at Extension Month 12
|
-14.54 μmol/L
Interval -14.54 to -14.54
|
9.12 μmol/L
Interval 9.12 to 9.12
|
—
|
|
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
Change at Extension Month 15
|
-12.83 μmol/L
Interval -12.83 to -12.83
|
24.51 μmol/L
Interval 24.51 to 24.51
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 42
|
2.50 μmol/L
Interval -2.57 to 9.37
|
-1.71 μmol/L
Interval -2.66 to 1.5
|
—
|
|
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
Change at Week 48
|
3.61 μmol/L
Interval -1.0 to 15.0
|
-2.36 μmol/L
Interval -6.08 to -1.14
|
—
|
|
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
Change at Week 6
|
2.53 μmol/L
Interval 0.0 to 7.25
|
-1.32 μmol/L
Interval -4.61 to 18.5
|
—
|
|
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
Change at Week 12
|
4.28 μmol/L
Interval 0.0 to 12.5
|
-1.14 μmol/L
Interval -3.0 to 1.71
|
—
|
|
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
Change at Week 18
|
2.99 μmol/L
Interval 0.5 to 14.2
|
-1.82 μmol/L
Interval -3.25 to 2.0
|
—
|
|
Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
0.93 μmol/L
Interval -1.0 to 6.1
|
-2.50 μmol/L
Interval -4.0 to -1.71
|
—
|
|
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
Change at Week 36
|
0.00 μmol/L
Interval -4.28 to 3.37
|
-1.57 μmol/L
Interval -2.5 to 0.0
|
—
|
|
Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Baseline
|
21.58 μmol/L
Interval 15.37 to 37.18
|
25.50 μmol/L
Interval 8.0 to 76.0
|
—
|
|
Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 3
|
0.00 μmol/L
Interval -6.04 to 1.5
|
-1.07 μmol/L
Interval -1.5 to 15.0
|
—
|
|
Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 24
|
1.00 μmol/L
Interval -1.0 to 15.0
|
-1.75 μmol/L
Interval -2.85 to 0.0
|
—
|
|
Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
3.37 μmol/L
Interval 0.0 to 4.28
|
-2.00 μmol/L
Interval -15.0 to 1.5
|
—
|
|
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
Change at Extension Month 6
|
0.00 μmol/L
Interval -5.99 to 19.67
|
-1.00 μmol/L
Interval -6.0 to 3.99
|
—
|
|
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
Change at Extension Month 9
|
—
|
-3.79 μmol/L
Interval -15.0 to 7.41
|
—
|
|
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
Change at Extension Month 12
|
-9.41 μmol/L
Interval -9.41 to -9.41
|
7.41 μmol/L
Interval 7.41 to 7.41
|
—
|
|
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
Change at Extension Month 15
|
-5.99 μmol/L
Interval -5.99 to -5.99
|
12.54 μmol/L
Interval 12.54 to 12.54
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 36
|
-26.0 unit per liter (U/L)
Interval -64.0 to -6.0
|
-4.0 unit per liter (U/L)
Interval -89.5 to 4.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 42
|
-24.0 unit per liter (U/L)
Interval -45.0 to -17.0
|
5.0 unit per liter (U/L)
Interval -87.0 to 9.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Baseline
|
216.0 unit per liter (U/L)
Interval 144.5 to 290.0
|
267.5 unit per liter (U/L)
Interval 151.0 to 381.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 3
|
-21.0 unit per liter (U/L)
Interval -48.0 to 6.0
|
-9.0 unit per liter (U/L)
Interval -48.0 to 0.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 6
|
-7.0 unit per liter (U/L)
Interval -22.0 to 19.0
|
5.0 unit per liter (U/L)
Interval -12.0 to 15.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 12
|
-1.0 unit per liter (U/L)
Interval -54.0 to 12.0
|
-17.0 unit per liter (U/L)
Interval -32.0 to 6.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 18
|
-20.5 unit per liter (U/L)
Interval -35.5 to 16.5
|
-4.5 unit per liter (U/L)
Interval -37.5 to 1.5
|
—
|
|
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
Change at Week 24
|
-30.0 unit per liter (U/L)
Interval -66.0 to 16.0
|
-5.0 unit per liter (U/L)
Interval -100.0 to 4.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
-34.5 unit per liter (U/L)
Interval -76.0 to -19.0
|
-20.0 unit per liter (U/L)
Interval -33.0 to -7.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
-29.0 unit per liter (U/L)
Interval -63.0 to -17.0
|
8.0 unit per liter (U/L)
Interval -3.0 to 13.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
-24.0 unit per liter (U/L)
Interval -48.0 to -7.0
|
10.0 unit per liter (U/L)
Interval -14.0 to 26.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 6
|
6.0 unit per liter (U/L)
Interval -33.0 to 7.0
|
-46.0 unit per liter (U/L)
Interval -133.0 to 41.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 9
|
—
|
-66.5 unit per liter (U/L)
Interval -148.0 to 15.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 12
|
-72.0 unit per liter (U/L)
Interval -72.0 to -72.0
|
122.0 unit per liter (U/L)
Interval 122.0 to 122.0
|
—
|
|
Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 15
|
-83.0 unit per liter (U/L)
Interval -83.0 to -83.0
|
10.0 unit per liter (U/L)
Interval 10.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Extension Month 3
|
-8.0 U/L
Interval -12.0 to -3.0
|
-1.0 U/L
Interval -7.0 to 7.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 6
|
-12.0 U/L
Interval -27.0 to -1.0
|
-1.5 U/L
Interval -6.0 to 3.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 9
|
—
|
-6.0 U/L
Interval -11.0 to -1.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 12
|
-34.0 U/L
Interval -34.0 to -34.0
|
-2.0 U/L
Interval -2.0 to -2.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 15
|
-32.0 U/L
Interval -32.0 to -32.0
|
1.0 U/L
Interval 1.0 to 1.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Baseline
|
47.5 U/L
Interval 31.0 to 60.5
|
38.0 U/L
Interval 27.0 to 56.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 3
|
-5.0 U/L
Interval -9.0 to -1.0
|
-2.0 U/L
Interval -9.0 to 1.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 6
|
-5.0 U/L
Interval -9.0 to 1.0
|
2.5 U/L
Interval -1.0 to 12.5
|
—
|
|
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
Change at Week 12
|
1.0 U/L
Interval -9.0 to 5.0
|
10.0 U/L
Interval 1.0 to 19.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 18
|
-6.5 U/L
Interval -12.5 to -3.5
|
-0.5 U/L
Interval -5.0 to 1.5
|
—
|
|
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
Change at Week 24
|
-4.0 U/L
Interval -5.0 to 4.0
|
-4.0 U/L
Interval -8.0 to 3.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
-6.0 U/L
Interval -12.0 to 3.0
|
1.5 U/L
Interval -2.0 to 3.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 36
|
11.5 U/L
Interval -6.0 to 24.0
|
-3.0 U/L
Interval -5.0 to 5.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 42
|
-9.0 U/L
Interval -12.0 to -3.0
|
-1.0 U/L
Interval -6.0 to 1.0
|
—
|
|
Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
-6.0 U/L
Interval -7.0 to -2.0
|
1.0 U/L
Interval -1.0 to 2.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Baseline
|
60.0 U/L
Interval 45.5 to 95.5
|
65.5 U/L
Interval 46.0 to 104.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 36
|
19.5 U/L
Interval -10.0 to 34.0
|
2.0 U/L
Interval -4.0 to 15.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 42
|
-3.5 U/L
Interval -14.0 to 8.0
|
1.0 U/L
Interval -2.0 to 39.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
-12.0 U/L
Interval -22.0 to 7.0
|
0.5 U/L
Interval -15.0 to 20.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 3
|
-4.0 U/L
Interval -11.0 to 3.0
|
-1.0 U/L
Interval -13.0 to 6.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 6
|
-4.0 U/L
Interval -12.0 to 0.5
|
10.5 U/L
Interval -3.5 to 23.5
|
—
|
|
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
Change at Week 12
|
0.0 U/L
Interval -5.0 to 19.0
|
18.0 U/L
Interval -3.0 to 29.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 18
|
-1.5 U/L
Interval -7.5 to 5.5
|
-5.0 U/L
Interval -10.5 to 4.5
|
—
|
|
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
Change at Week 24
|
-7.0 U/L
Interval -13.0 to -2.0
|
-2.0 U/L
Interval -7.0 to 1.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
-10.0 U/L
Interval -12.0 to -3.0
|
1.0 U/L
Interval -2.0 to 9.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
-6.5 U/L
Interval -11.0 to 6.0
|
-12.0 U/L
Interval -15.0 to 6.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 6
|
-16.0 U/L
Interval -32.0 to 1.0
|
-0.5 U/L
Interval -21.0 to 20.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 9
|
—
|
-8.5 U/L
Interval -33.0 to 16.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 12
|
-33.0 U/L
Interval -33.0 to -33.0
|
19.0 U/L
Interval 19.0 to 19.0
|
—
|
|
Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 15
|
-34.0 U/L
Interval -34.0 to -34.0
|
16.0 U/L
Interval 16.0 to 16.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 3
|
-12.5 U/L
Interval -27.0 to -2.0
|
-13.5 U/L
Interval -54.0 to -1.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 6
|
-11.0 U/L
Interval -28.0 to -3.0
|
0.0 U/L
Interval -31.0 to 4.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 24
|
8.0 U/L
Interval -37.0 to 25.0
|
-14.0 U/L
Interval -70.0 to -5.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
-9.0 U/L
Interval -22.0 to -5.0
|
-12.5 U/L
Interval -27.0 to 5.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 36
|
-5.5 U/L
Interval -12.0 to 24.0
|
-10.5 U/L
Interval -90.0 to 4.5
|
—
|
|
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
Change at Week 48
|
-9.0 U/L
Interval -21.0 to -6.0
|
-15.0 U/L
Interval -112.0 to 9.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
-9.5 U/L
Interval -48.0 to 1.0
|
9.0 U/L
Interval -14.0 to 22.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 6
|
-10.0 U/L
Interval -35.0 to -9.0
|
-58.5 U/L
Interval -137.0 to 20.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 12
|
-13.0 U/L
Interval -32.0 to -3.0
|
-2.0 U/L
Interval -44.0 to 7.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 18
|
-9.5 U/L
Interval -28.0 to -0.5
|
-3.5 U/L
Interval -38.5 to 1.5
|
—
|
|
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
Change at Week 42
|
-12.0 U/L
Interval -26.0 to 5.0
|
-4.0 U/L
Interval -154.0 to 17.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 9
|
—
|
-57.0 U/L
Interval -128.0 to 14.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 12
|
-74.0 U/L
Interval -74.0 to -74.0
|
8.0 U/L
Interval 8.0 to 8.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 15
|
-63.0 U/L
Interval -63.0 to -63.0
|
2.0 U/L
Interval 2.0 to 2.0
|
—
|
|
Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Baseline
|
98.0 U/L
Interval 36.0 to 152.0
|
103.0 U/L
Interval 53.0 to 191.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 12
|
0.08 INR
Interval 0.0 to 0.15
|
-0.05 INR
Interval -0.1 to 0.0
|
—
|
|
Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 18
|
0.09 INR
Interval 0.0 to 0.1
|
-0.05 INR
Interval -0.13 to 0.05
|
—
|
|
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
Baseline
|
1.15 INR
Interval 1.1 to 1.2
|
1.23 INR
Interval 1.1 to 1.3
|
—
|
|
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
Change at Week 3
|
0.00 INR
Interval 0.0 to 0.1
|
0.00 INR
Interval 0.0 to 0.1
|
—
|
|
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
Change at Week 6
|
0.00 INR
Interval -0.03 to 0.0
|
0.00 INR
Interval -0.05 to 0.0
|
—
|
|
Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 24
|
0.03 INR
Interval -0.02 to 0.08
|
-0.05 INR
Interval -0.1 to 0.05
|
—
|
|
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
Change at Week 30
|
0.03 INR
Interval -0.03 to 0.1
|
0.00 INR
Interval -0.1 to 0.0
|
—
|
|
Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 36
|
0.05 INR
Interval 0.0 to 0.1
|
-0.10 INR
Interval -0.18 to 0.03
|
—
|
|
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
Change at Week 42
|
0.05 INR
Interval 0.0 to 0.07
|
0.00 INR
Interval -0.1 to 0.05
|
—
|
|
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
Change at Week 48
|
0.00 INR
Interval -0.03 to 0.05
|
-0.10 INR
Interval -0.15 to 0.0
|
—
|
|
Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
0.06 INR
Interval 0.0 to 0.1
|
-0.10 INR
Interval -0.1 to -0.1
|
—
|
|
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
Change at Extension Month 6
|
0.05 INR
Interval -0.1 to 0.15
|
-0.05 INR
Interval -0.1 to 0.0
|
—
|
|
Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 9
|
0.15 INR
Interval 0.15 to 0.15
|
0.00 INR
Interval 0.0 to 0.0
|
—
|
|
Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 12
|
0.05 INR
Interval 0.05 to 0.05
|
0.10 INR
Interval 0.1 to 0.1
|
—
|
|
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
Change at Extension Month 15
|
0.05 INR
Interval 0.05 to 0.05
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Baseline
|
60.000 µmol/L
Interval 51.0 to 96.732
|
60.172 µmol/L
Interval 55.0 to 95.472
|
—
|
|
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
Change at Week 3
|
0.884 µmol/L
Interval -3.0 to 5.0
|
-0.308 µmol/L
Interval -2.0 to 1.768
|
—
|
|
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
Change at Week 6
|
5.000 µmol/L
Interval 0.388 to 5.746
|
0.884 µmol/L
Interval -1.0 to 4.0
|
—
|
|
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 12
|
-0.496 µmol/L
Interval -4.0 to 13.5
|
2.500 µmol/L
Interval -1.0 to 5.0
|
—
|
|
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 18
|
-2.431 µmol/L
Interval -4.958 to 7.25
|
0.942 µmol/L
Interval -6.17 to 5.036
|
—
|
|
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
Change at Week 24
|
-1.000 µmol/L
Interval -4.0 to -0.496
|
-2.652 µmol/L
Interval -11.492 to 5.0
|
—
|
|
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
-0.663 µmol/L
Interval -4.032 to 1.768
|
-2.250 µmol/L
Interval -6.188 to 3.0
|
—
|
|
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 36
|
1.500 µmol/L
Interval -1.326 to 7.0
|
2.466 µmol/L
Interval -1.96 to 33.586
|
—
|
|
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
Change at Week 42
|
2.000 µmol/L
Interval -1.326 to 4.0
|
6.236 µmol/L
Interval -2.652 to 28.0
|
—
|
|
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
2.221 µmol/L
Interval -3.536 to 6.0
|
0.466 µmol/L
Interval -3.0 to 20.0
|
—
|
|
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
3.884 µmol/L
Interval 0.0 to 6.63
|
0.000 µmol/L
Interval -1.5 to 12.0
|
—
|
|
Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 6
|
2.652 µmol/L
Interval -4.0 to 12.818
|
4.648 µmol/L
Interval -7.5 to 16.796
|
—
|
|
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
Change at Extension Month 9
|
—
|
15.068 µmol/L
Interval 4.5 to 25.636
|
—
|
|
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
Change at Extension Month 12
|
10.608 µmol/L
Interval 10.608 to 10.608
|
27.404 µmol/L
Interval 27.404 to 27.404
|
—
|
|
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
Change at Extension Month 15
|
4.420 µmol/L
Interval 4.42 to 4.42
|
29.172 µmol/L
Interval 29.172 to 29.172
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=12 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Baseline
|
34.50 g/L
Interval 33.0 to 36.75
|
33.00 g/L
Interval 30.0 to 36.5
|
—
|
|
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
Change at Week 3
|
-2.25 g/L
Interval -2.5 to -1.0
|
-0.50 g/L
Interval -1.7 to 0.0
|
—
|
|
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 6
|
-1.00 g/L
Interval -3.0 to 0.0
|
0.00 g/L
Interval -1.0 to 1.3
|
—
|
|
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
Change at Week 12
|
-2.00 g/L
Interval -4.0 to -1.5
|
-0.70 g/L
Interval -1.0 to 1.5
|
—
|
|
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
Change at Week 18
|
-4.25 g/L
Interval -5.0 to -1.5
|
0.00 g/L
Interval -1.6 to 0.5
|
—
|
|
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
Change at Week 24
|
-2.50 g/L
Interval -4.0 to -1.0
|
-2.50 g/L
Interval -2.7 to 1.0
|
—
|
|
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 30
|
-2.50 g/L
Interval -4.0 to -2.0
|
0.15 g/L
Interval -1.5 to 1.0
|
—
|
|
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 36
|
-2.00 g/L
Interval -3.0 to -2.0
|
0.50 g/L
Interval -2.35 to 2.25
|
—
|
|
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
Change at Week 42
|
-1.25 g/L
Interval -4.0 to 0.0
|
-0.70 g/L
Interval -1.0 to 2.0
|
—
|
|
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
-0.50 g/L
Interval -2.0 to 1.0
|
0.50 g/L
Interval -4.7 to 1.0
|
—
|
|
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 3
|
-2.50 g/L
Interval -3.0 to -1.0
|
1.00 g/L
Interval -2.7 to 2.5
|
—
|
|
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
Change at Extension Month 6
|
-2.00 g/L
Interval -3.0 to -1.0
|
-0.35 g/L
Interval -1.7 to 1.0
|
—
|
|
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 9
|
—
|
-1.35 g/L
Interval -3.7 to 1.0
|
—
|
|
Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Extension Month 12
|
-1.00 g/L
Interval -1.0 to -1.0
|
-2.70 g/L
Interval -2.7 to -2.7
|
—
|
|
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
Change at Extension Month 15
|
-1.00 g/L
Interval -1.0 to -1.0
|
-11.70 g/L
Interval -11.7 to -11.7
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=11 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=9 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Baseline
|
141.5 10^9/L
Interval 80.0 to 160.5
|
132.5 10^9/L
Interval 84.5 to 158.5
|
—
|
|
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
Change at Week 3
|
-6.2 10^9/L
Interval -21.0 to -3.0
|
-7.5 10^9/L
Interval -12.0 to 8.5
|
—
|
|
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
Change at Week 6
|
-12.0 10^9/L
Interval -28.8 to -2.3
|
15.0 10^9/L
Interval 1.0 to 26.5
|
—
|
|
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
Change at Week 12
|
-10.5 10^9/L
Interval -31.0 to 7.5
|
-15.0 10^9/L
Interval -15.0 to -1.5
|
—
|
|
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
Change at Week 18
|
-15.0 10^9/L
Interval -21.9 to -8.5
|
7.5 10^9/L
Interval -10.0 to 38.5
|
—
|
|
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
Change at Week 24
|
4.5 10^9/L
Interval -14.4 to 17.0
|
-1.5 10^9/L
Interval -25.0 to 25.5
|
—
|
|
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
Change at Week 30
|
-11.4 10^9/L
Interval -23.5 to 15.0
|
-5.5 10^9/L
Interval -9.0 to 6.5
|
—
|
|
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
Change at Week 36
|
-16.5 10^9/L
Interval -20.5 to -12.0
|
9.8 10^9/L
Interval -6.5 to 39.5
|
—
|
|
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
Change at Week 42
|
-16.2 10^9/L
Interval -37.5 to -10.0
|
9.0 10^9/L
Interval 6.5 to 11.0
|
—
|
|
Change From Baseline in Platelets at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Change at Week 48
|
4.0 10^9/L
Interval -41.5 to 23.0
|
-9.0 10^9/L
Interval -11.5 to 14.5
|
—
|
|
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
Change at Extension Month 3
|
-5.0 10^9/L
Interval -24.0 to 16.5
|
-11.5 10^9/L
Interval -24.0 to -8.5
|
—
|
|
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
Change at Extension Month 6
|
48.5 10^9/L
Interval 14.0 to 78.0
|
-0.5 10^9/L
Interval -0.5 to -0.5
|
—
|
|
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
Change at Extension Month 9
|
—
|
-4.5 10^9/L
Interval -5.5 to -3.5
|
—
|
|
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
Change at Extension Month 12
|
-2.0 10^9/L
Interval -2.0 to -2.0
|
-3.5 10^9/L
Interval -3.5 to -3.5
|
—
|
|
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
Change at Extension Month 15
|
-9.0 10^9/L
Interval -9.0 to -9.0
|
-22.5 10^9/L
Interval -22.5 to -22.5
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Total bile acids (micromole \[μM\]) = total ursodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total cholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=11 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Baseline
|
149 μM
Interval 90.3 to 307.0
|
127 μM
Interval 65.3 to 176.0
|
—
|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 6
|
16.3 μM
Interval -7.68 to 37.4
|
8.09 μM
Interval -15.9 to 37.1
|
—
|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 12
|
0.863 μM
Interval -21.0 to 88.4
|
5.55 μM
Interval -58.4 to 13.7
|
—
|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 18
|
17.7 μM
Interval -56.0 to 160.0
|
12.8 μM
Interval -169.0 to 36.0
|
—
|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 24
|
3.29 μM
Interval -76.6 to 30.6
|
-3.14 μM
Interval -14.5 to 21.3
|
—
|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 30
|
26.0 μM
Interval -56.0 to 98.5
|
16.1 μM
Interval -7.06 to 38.7
|
—
|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 36
|
-15.2 μM
Interval -79.4 to 10.0
|
-1.54 μM
Interval -22.9 to 24.6
|
—
|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 48
|
63.2 μM
Interval 16.7 to 132.0
|
0.876 μM
Interval -4.07 to 19.5
|
—
|
|
Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Extension Month 3
|
—
|
-32.9 μM
Interval -32.9 to -32.9
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
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, glyco-conjugate, tauro-conjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=11 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 12
|
-3.97 μM
Interval -13.3 to 63.9
|
1.46 μM
Interval -5.43 to 4.81
|
—
|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 18
|
-5.00 μM
Interval -20.2 to 51.0
|
3.98 μM
Interval -18.3 to 7.21
|
—
|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Baseline
|
64.7 μM
Interval 29.4 to 75.2
|
42.1 μM
Interval 18.6 to 69.6
|
—
|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 6
|
-4.98 μM
Interval -6.88 to 36.2
|
3.58 μM
Interval -5.64 to 14.0
|
—
|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 24
|
-6.76 μM
Interval -18.5 to -1.25
|
3.18 μM
Interval -2.53 to 15.2
|
—
|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 30
|
6.74 μM
Interval -6.22 to 7.44
|
1.47 μM
Interval -3.87 to 13.6
|
—
|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 36
|
-5.74 μM
Interval -24.9 to -0.576
|
-2.69 μM
Interval -14.4 to 9.66
|
—
|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 48
|
10.9 μM
Interval 6.32 to 19.8
|
4.18 μM
Interval -2.08 to 9.82
|
—
|
|
Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Extension Month 3
|
—
|
-9.57 μM
Interval -9.57 to -9.57
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=11 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 6
|
0.0990 ng/mL
Interval -0.0445 to 0.296
|
0.0770 ng/mL
Interval -0.11 to 0.45
|
—
|
|
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
Change at Week 12
|
-0.0275 ng/mL
Interval -0.069 to 0.156
|
-0.289 ng/mL
Interval -1.31 to 0.01
|
—
|
|
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
Change at Week 18
|
-0.0470 ng/mL
Interval -0.278 to 0.205
|
-0.267 ng/mL
Interval -0.965 to 8.05
|
—
|
|
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
Baseline
|
0.708 ng/mL
Interval 0.372 to 5.16
|
0.814 ng/mL
Interval 0.472 to 2.09
|
—
|
|
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
Change at Week 24
|
-0.00100 ng/mL
Interval -0.007 to 0.692
|
-0.141 ng/mL
Interval -1.67 to 1.07
|
—
|
|
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
Change at Week 30
|
0.0890 ng/mL
Interval 0.05 to 0.355
|
-0.386 ng/mL
Interval -1.77 to 2.5
|
—
|
|
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
Change at Week 36
|
0.118 ng/mL
Interval -0.104 to 0.24
|
-0.476 ng/mL
Interval -3.53 to 5.41
|
—
|
|
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
Change at Week 48
|
-0.170 ng/mL
Interval -0.491 to -0.014
|
-0.510 ng/mL
Interval -1.83 to 5.2
|
—
|
|
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
Change at Extension Month 3
|
—
|
1.36 ng/mL
Interval 1.36 to 1.36
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3Population: Participants in the ITT population with available data were analyzed. Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
Outcome measures
| Measure |
OCA 5 mg Once Weekly
n=11 Participants
Participants received OCA 5 mg tablets orally once weekly.
|
OCA 5 mg Twice Weekly
n=10 Participants
Participants received OCA 5 mg tablets orally twice weekly.
|
OCA 10 mg Twice Weekly
Participants received OCA 10 mg tablets orally twice weekly.
|
|---|---|---|---|
|
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
Change at Week 18
|
-57.0 picograms per milliliter (pg/mL)
Interval -118.0 to 40.0
|
136 picograms per milliliter (pg/mL)
Interval -28.3 to 298.0
|
—
|
|
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 24
|
-33.0 picograms per milliliter (pg/mL)
Interval -152.0 to 402.0
|
16.6 picograms per milliliter (pg/mL)
Interval -24.0 to 219.0
|
—
|
|
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 30
|
-83.0 picograms per milliliter (pg/mL)
Interval -123.0 to 43.0
|
142 picograms per milliliter (pg/mL)
Interval -45.0 to 168.0
|
—
|
|
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Baseline
|
278 picograms per milliliter (pg/mL)
Interval 105.0 to 618.0
|
163 picograms per milliliter (pg/mL)
Interval 139.0 to 359.0
|
—
|
|
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 6
|
-50.7 picograms per milliliter (pg/mL)
Interval -142.0 to 33.0
|
26.0 picograms per milliliter (pg/mL)
Interval 4.5 to 101.0
|
—
|
|
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 12
|
-14.0 picograms per milliliter (pg/mL)
Interval -220.0 to 19.0
|
119 picograms per milliliter (pg/mL)
Interval -25.6 to 174.0
|
—
|
|
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 36
|
26.0 picograms per milliliter (pg/mL)
Interval -34.0 to 102.0
|
15.0 picograms per milliliter (pg/mL)
Interval -97.4 to 201.0
|
—
|
|
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Week 48
|
-28.5 picograms per milliliter (pg/mL)
Interval -161.0 to 84.5
|
69.6 picograms per milliliter (pg/mL)
Interval 8.0 to 145.0
|
—
|
|
Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Change at Extension Month 3
|
-117 picograms per milliliter (pg/mL)
Interval -117.0 to -117.0
|
0 picograms per milliliter (pg/mL)
Interval 0.0 to 0.0
|
—
|
Adverse Events
Placebo
Serious events: 9 serious events
Other events: 10 other events
Deaths: 2 deaths
Obeticholic Acid (OCA)
Serious events: 7 serious events
Other events: 10 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Placebo
n=12 participants at risk
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).
|
Obeticholic Acid (OCA)
n=10 participants at risk
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).
|
|---|---|---|
|
Infections and infestations
COVID-19
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
30.0%
3/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Ascites
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Pyrexia
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Hepatic encephalopathy
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Renal and urinary disorders
Acute kidney injury
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Surgical and medical procedures
Liver transplant
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Vascular disorders
Aortic aneurysm rupture
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
Other adverse events
| Measure |
Placebo
n=12 participants at risk
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).
|
Obeticholic Acid (OCA)
n=10 participants at risk
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).
|
|---|---|---|
|
Gastrointestinal disorders
Ascites
|
33.3%
4/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
60.0%
6/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Abdominal distension
|
25.0%
3/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Abdominal pain
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Nausea
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Frequent bowel movements
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Constipation
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Dry mouth
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Gastric antral vascular ectasia
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Gastric polyps
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Large intestine polyp
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Portal hypertensive gastropathy
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Toothache
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Gastrointestinal disorders
Varices oesophageal
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Urinary tract infection
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
30.0%
3/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Cytomegalovirus infection reactivation
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Oesophageal candidiasis
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Peritonitis bacterial
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Cellulitis
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Ear infection
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Fungal infection
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Influenza
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Infections and infestations
Skin infection
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Fatigue
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Chest discomfort
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Disease progression
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Oedema peripheral
|
33.3%
4/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Asthenia
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Non-cardiac chest pain
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
General disorders
Pyrexia
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Metabolism and nutrition disorders
Dehydration
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Burning sensation
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Encephalopathy
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Hypoaesthesia
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Memory impairment
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Nervous system disorders
Sciatica
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
30.0%
3/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Skin and subcutaneous tissue disorders
Palmar erythema
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
30.0%
3/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Musculoskeletal and connective tissue disorders
Limb mass
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Cardiac disorders
Palpitations
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Investigations
Blood bilirubin increased
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Investigations
Blood urea increased
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Investigations
Cardiac murmur
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Renal and urinary disorders
Acute kidney injury
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
20.0%
2/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Endocrine disorders
Thyroid mass
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Eye disorders
Vitreous floaters
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Eye disorders
Vision blurred
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Injury, poisoning and procedural complications
Joint injury
|
16.7%
2/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Reproductive system and breast disorders
Breast pain
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Vascular disorders
Peripheral coldness
|
0.00%
0/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
10.0%
1/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Vascular disorders
Haematoma
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
|
Vascular disorders
Haemorrhage
|
8.3%
1/12 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
0.00%
0/10 • Baseline up to approximately 3 years
The Safety Population included all participants who received at least 1 dose of investigational product (OCA or placebo). Data were prespecified to be collected per randomization arm (OCA or placebo). Data at the separate dose levels are not available.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Principal Investigators must wait 18 months after the study ends to publish their results and a multi-center publication must come first. The sponsor has a 45 day review period with the option to extend to an additional 90 days.
- Publication restrictions are in place
Restriction type: OTHER