Trial Outcomes & Findings for Phase 2 Study on Effects of Obeticholic Acid (OCA) on Lipoprotein Metabolism in Participants With Primary Biliary Cirrhosis (NCT NCT01865812)

NCT ID: NCT01865812

Last Updated: 2022-08-24

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 27 participants
• Primary outcome timeframe: Baseline, Week 8
• Results posted on: 2022-08-24

Participant Flow

Recruitment started 19-Nov-2013 and completed 16-May-2014 in the primary treatment phase (PTP). Thirty-three participants were screened and 27 enrolled.

Screening window was up to 20 days in duration to assess eligibility. Stable dose of ursodeoxycholic acid (UDCA) for 3 months prior to Day 0 was required. A 28-day washout period for bile acid sequestrants and no serum-lipid modifying agents for 3 months prior to Day 0 was also required. After the PTP, participants were offered the opportunity to enter the open-label, long-term safety extension (LTSE) phase of the study.

Participant milestones

Measure	Primary Treatment Phase All participants were treated with obeticholic acid (OCA) (oral administration, 10 milligrams \[mg\], once daily \[QD\]) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.
Primary Treatment Phase STARTED	27	0
Primary Treatment Phase Received at Least 1 Dose of Study Drug	27	0
Primary Treatment Phase COMPLETED	25	0
Primary Treatment Phase NOT COMPLETED	2	0
Long-term Safety Extension Phase STARTED	0	21
Long-term Safety Extension Phase Received at Least 1 Dose of Study Drug	0	21
Long-term Safety Extension Phase COMPLETED	0	15
Long-term Safety Extension Phase NOT COMPLETED	0	6

Reasons for withdrawal

Measure	Primary Treatment Phase All participants were treated with obeticholic acid (OCA) (oral administration, 10 milligrams \[mg\], once daily \[QD\]) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.
Primary Treatment Phase Adverse Event	2	0
Long-term Safety Extension Phase Withdrawal by Subject	0	1
Long-term Safety Extension Phase Pruritus	0	3
Long-term Safety Extension Phase Physician Decision	0	1
Long-term Safety Extension Phase Participant Unavailable for Final Study Visit	0	1

Baseline Characteristics

Phase 2 Study on Effects of Obeticholic Acid (OCA) on Lipoprotein Metabolism in Participants With Primary Biliary Cirrhosis

Baseline characteristics by cohort

Measure	Obeticholic Acid n=26 Participants All participants were treated with OCA (oral administration, 10 mg, QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, eligible participants entered the open-label LTSE phase and received 10 mg OCA QD for up to 2 years.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Age, Continuous	56.5 years STANDARD_DEVIATION 9.15 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race/Ethnicity, Customized White	25 participants n=5 Participants
Race/Ethnicity, Customized Non-White/Hispanic	1 participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants
High-density Lipoprotein (HDL) Cholesterol Concentration	1.86 mmol/L STANDARD_DEVIATION 0.51798 • n=5 Participants
HDL Particle Size	10.19 nm STANDARD_DEVIATION 0.734 • n=5 Participants
HDL Particle Concentration (total)	30.08 µmol/L STANDARD_DEVIATION 7.228 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=23 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Absolute Change From Baseline In High-density Lipoprotein (HDL) Cholesterol Concentration	—	-0.38 mmol/L Interval -0.51 to -0.24

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=23 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Absolute Change From Baseline In HDL Particle Size	—	-0.44 nm Interval -0.63 to -0.25

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=23 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Absolute Change From Baseline In HDL Particle Number	—	-0.06 umol/L Interval -1.58 to 1.46

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In HDL Cholesterol Concentration At Weeks 4, 8, and 12 Week 4	—	-0.2072 mmol/L Interval -0.5957 to -0.0259
Median Change From Baseline In HDL Cholesterol Concentration At Weeks 4, 8, and 12 Week 8	—	-0.3108 mmol/L Interval -0.4403 to -0.0777
Median Change From Baseline In HDL Cholesterol Concentration At Weeks 4, 8, and 12 Week 12	—	0.0518 mmol/L Interval -0.2849 to 0.1554

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In HDL Particle Size At Weeks 4, 8, and 12 Week 4	—	-0.30 nm Interval -0.5 to -0.1
Median Change From Baseline In HDL Particle Size At Weeks 4, 8, and 12 Week 8	—	-0.30 nm Interval -0.6 to -0.1
Median Change From Baseline In HDL Particle Size At Weeks 4, 8, and 12 Week 12	—	0.00 nm Interval -0.2 to 0.1

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8, Week 12

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In HDL Particle Number At Weeks 4, 8, and 12 Week 4	—	0.55 umol/L Interval -2.6 to 1.6
Median Change From Baseline In HDL Particle Number At Weeks 4, 8, and 12 Week 8	—	0.60 umol/L Interval -1.6 to 1.7
Median Change From Baseline In HDL Particle Number At Weeks 4, 8, and 12 Week 12	—	1.60 umol/L Interval -1.6 to 3.1

SECONDARY outcome

Timeframe: Week 8, Week 12

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=22 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Week 8 In HDL Cholesterol Concentration At Week 12	—	0.3108 mmol/L Interval 0.1036 to 0.518

SECONDARY outcome

Timeframe: Week 8, Week 12

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=22 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Week 8 In HDL Particle Size At Week 12	—	0.30 nm Interval 0.1 to 0.5

SECONDARY outcome

Timeframe: Week 8, Week 12

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=22 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Week 8 In HDL Particle Number At Week 12	—	1.40 umol/L Interval -0.6 to 3.1

SECONDARY outcome

Timeframe: Week 8

Population: The PK Population was comprised of all subjects who had at least 1 confirmed analyzable fasting sample at Week 8 and who did not have any major protocol deviations that potentially affected exposure levels. The PK Population was used for the OCA PK and bile acid analyses.

Results are reported in nanograms per milliliter (ng/mL).

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=7 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Maximum Plasma Concentration (Cmax) Of OCA And Conjugates Taurine Conjugate (Tauro)-OCA	—	219 ng/mL Standard Deviation 208
Maximum Plasma Concentration (Cmax) Of OCA And Conjugates OCA	—	107 ng/mL Standard Deviation 112
Maximum Plasma Concentration (Cmax) Of OCA And Conjugates Glycine Conjugate (Glyco)-OCA	—	212 ng/mL Standard Deviation 144
Maximum Plasma Concentration (Cmax) Of OCA And Conjugates Total-OCA	—	409 ng/mL Standard Deviation 299

SECONDARY outcome

Timeframe: Week 8

Population: The PK Population was comprised of all subjects who had at least 1 confirmed analyzable fasting sample at Week 8 and who did not have any major protocol deviations that potentially affected exposure levels. The PK Population was used for the OCA PK and bile acid analyses.

Results are reported in hours (h).

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=7 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Time To Reach Cmax (Tmax) For OCA And Conjugates OCA	—	1.00 h Interval 0.75 to 4.0
Time To Reach Cmax (Tmax) For OCA And Conjugates Glyco-OCA	—	5.00 h Interval 1.5 to 6.0
Time To Reach Cmax (Tmax) For OCA And Conjugates Tauro-OCA	—	5.98 h Interval 5.0 to 6.0
Time To Reach Cmax (Tmax) For OCA And Conjugates Total-OCA	—	5.00 h Interval 1.0 to 6.0

SECONDARY outcome

Timeframe: Week 8

Population: The PK Population was comprised of all subjects who had at least 1 confirmed analyzable fasting sample at Week 8 and who did not have any major protocol deviations that potentially affected exposure levels. The PK Population was used for the OCA PK and bile acid analyses.

Results are reported in hour*nanograms per milliliter (h*ng/mL).

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=7 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Area Under The Concentration-time Curve From Hour 0 To Last Sampling Time (Hour 6) (AUC0-6) For OCA And Conjugates OCA	—	189 h*ng/mL Standard Deviation 185
Area Under The Concentration-time Curve From Hour 0 To Last Sampling Time (Hour 6) (AUC0-6) For OCA And Conjugates Glyco-OCA	—	702 h*ng/mL Standard Deviation 644
Area Under The Concentration-time Curve From Hour 0 To Last Sampling Time (Hour 6) (AUC0-6) For OCA And Conjugates Tauro-OCA	—	698 h*ng/mL Standard Deviation 653
Area Under The Concentration-time Curve From Hour 0 To Last Sampling Time (Hour 6) (AUC0-6) For OCA And Conjugates Total-OCA	—	1360 h*ng/mL Standard Deviation 1150

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total Cholesterol Week 4	—	-0.0518 mmol/L Interval -0.8806 to 0.259
Median Change From Baseline In Total Cholesterol Week 8/EOT	—	-0.2849 mmol/L Interval -0.777 to 0.0777
Median Change From Baseline In Total Cholesterol Week 12	—	0.2331 mmol/L Interval -0.3885 to 0.4662
Median Change From Baseline In Total Cholesterol Month 6	-0.1813 mmol/L Interval -0.8806 to 0.1295	—
Median Change From Baseline In Total Cholesterol Month 12	0.0777 mmol/L Interval -0.1554 to 0.5698	—
Median Change From Baseline In Total Cholesterol Month 18	0.2849 mmol/L Interval -0.259 to 0.9842	—
Median Change From Baseline In Total Cholesterol Month 24/EOT	-0.0777 mmol/L Interval -0.4144 to 0.2849	—
Median Change From Baseline In Total Cholesterol Last Dose	0.285 mmol/L Interval -0.259 to 0.699	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total Triglycerides Week 4	—	-0.0226 mmol/L Interval -0.226 to 0.0678
Median Change From Baseline In Total Triglycerides Week 8/EOT	—	0.0565 mmol/L Interval -0.113 to 0.2373
Median Change From Baseline In Total Triglycerides Week 12	—	0.1130 mmol/L Interval -0.0113 to 0.2147
Median Change From Baseline In Total Triglycerides Month 6	-0.1469 mmol/L Interval -0.4633 to 0.0791	—
Median Change From Baseline In Total Triglycerides Month 12	-0.0113 mmol/L Interval -0.2938 to 0.226	—
Median Change From Baseline In Total Triglycerides Month 18	-0.0565 mmol/L Interval -0.2034 to 0.226	—
Median Change From Baseline In Total Triglycerides Month 24/EOT	0.000 mmol/L Interval -0.226 to 0.113	—
Median Change From Baseline In Total Triglycerides Last Dose	-0.068 mmol/L Interval -0.26 to 0.226	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) Week 4	—	0.27 mmol/L Interval 0.21 to 0.36
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) Week 8/EOT	—	0.31 mmol/L Interval 0.05 to 0.41
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) Week 12	—	0.18 mmol/L Interval -0.21 to 0.39
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) Month 6	0.3108 mmol/L Interval -0.0777 to 0.6216	—
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) Month 12	0.4403 mmol/L Interval 0.1036 to 0.7511	—
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) Month 18	0.5957 mmol/L Interval 0.1813 to 1.036	—
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) Month 24/EOT	0.3108 mmol/L Interval 0.1295 to 0.6216	—
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) Last Dose	0.518 mmol/L Interval 0.233 to 0.648	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In LDL Particle Size Week 4	—	-0.30 nm Interval -0.5 to -0.1
Median Change From Baseline In LDL Particle Size Week 8/EOT	—	-0.10 nm Interval -0.4 to 0.1
Median Change From Baseline In LDL Particle Size Week 12	—	0.00 nm Interval -0.3 to 0.2
Median Change From Baseline In LDL Particle Size Month 6	-0.10 nm Interval -0.3 to 0.3	—
Median Change From Baseline In LDL Particle Size Month 12	-0.20 nm Interval -0.5 to 0.3	—
Median Change From Baseline In LDL Particle Size Month 18	-0.10 nm Interval -0.5 to 0.1	—
Median Change From Baseline In LDL Particle Size Month 24/EOT	-0.10 nm Interval -0.2 to 0.2	—
Median Change From Baseline In LDL Particle Size Last Dose	-0.10 nm Interval -0.5 to 0.1	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Results are reported in nanomoles per liter (nmol/L).

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total LDL Particles Week 4	—	108.0 nmol/L Interval 73.0 to 231.0
Median Change From Baseline In Total LDL Particles Week 8/EOT	—	128.0 nmol/L Interval 57.0 to 273.0
Median Change From Baseline In Total LDL Particles Week 12	—	159.0 nmol/L Interval 18.0 to 197.0
Median Change From Baseline In Total LDL Particles Month 6 (Small)	148.0 nmol/L Interval -17.0 to 295.0	—
Median Change From Baseline In Total LDL Particles Month 12 (Small)	89.0 nmol/L Interval -13.0 to 318.0	—
Median Change From Baseline In Total LDL Particles Month 18 (Small)	18.0 nmol/L Interval -15.0 to 261.0	—
Median Change From Baseline In Total LDL Particles Month 24/EOT (Small)	34.0 nmol/L Interval -5.0 to 74.0	—
Median Change From Baseline In Total LDL Particles Last Dose (Small)	22.0 nmol/L Interval -23.0 to 98.0	—
Median Change From Baseline In Total LDL Particles Month 6 (Large)	9.0 nmol/L Interval -102.0 to 138.0	—
Median Change From Baseline In Total LDL Particles Month 12 (Large)	-53.0 nmol/L Interval -190.0 to 155.0	—
Median Change From Baseline In Total LDL Particles Month 18 (Large)	-18.0 nmol/L Interval -199.0 to 143.0	—
Median Change From Baseline In Total LDL Particles Month 24/EOT (Large)	-122.0 nmol/L Interval -229.0 to 60.0	—
Median Change From Baseline In Total LDL Particles Last Dose (Large)	-8.0 nmol/L Interval -243.0 to 162.0	—
Median Change From Baseline In Total LDL Particles Month 6 (Intermediate-density Lipoprotein [IDL])	-12.0 nmol/L Interval -121.0 to 72.0	—
Median Change From Baseline In Total LDL Particles Month 12 (IDL)	-57.0 nmol/L Interval -117.0 to 21.0	—
Median Change From Baseline In Total LDL Particles Month 18 (IDL)	-43.0 nmol/L Interval -104.0 to 112.0	—
Median Change From Baseline In Total LDL Particles Month 24/EOT (IDL)	78.0 nmol/L Interval -17.0 to 151.0	—
Median Change From Baseline In Total LDL Particles Last Dose (IDL)	11.0 nmol/L Interval -89.0 to 129.0	—

SECONDARY outcome

Timeframe: Baseline, Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Results are reported in milligrams per deciliter (mg/dL).

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=25 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol Week 12	—	5.0 mg/dL Interval -3.0 to 7.0
Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol Month 6	-21.0 mg/dL Interval -41.0 to 7.0	—
Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol Month 12	-7.0 mg/dL Interval -29.0 to 7.0	—
Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol Month 18	-14.0 mg/dL Interval -25.0 to 3.0	—
Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol Month 24/EOT	-1.0 mg/dL Interval -8.0 to 15.0	—
Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol Last Dose	-11.5 mg/dL Interval -29.0 to 3.0	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=21 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In VLDL Particle Size Month 6	-4.80 nm Interval -9.5 to 0.9	—
Median Change From Baseline In VLDL Particle Size Week 4	—	42.55 nm Interval 39.2 to 44.75
Median Change From Baseline In VLDL Particle Size Week 8/EOT	—	43.40 nm Interval 39.7 to 45.9
Median Change From Baseline In VLDL Particle Size Week 12	—	45.10 nm Interval 43.3 to 48.4
Median Change From Baseline In VLDL Particle Size Month 12	-3.50 nm Interval -8.2 to 0.5	—
Median Change From Baseline In VLDL Particle Size Month 18	-4.90 nm Interval -6.0 to 2.9	—
Median Change From Baseline In VLDL Particle Size Month 24/EOT	0.50 nm Interval -2.05 to 5.2	—
Median Change From Baseline In VLDL Particle Size Last Dose	-4.10 nm Interval -5.95 to 1.75	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=21 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In VLDL Particles Week 4	—	-5.55 nmol/L Interval -17.2 to -1.6
Median Change From Baseline In VLDL Particles Week 8/EOT	—	2.70 nmol/L Interval -14.8 to 9.1
Median Change From Baseline In VLDL Particles Week 12	—	-0.90 nmol/L Interval -9.5 to 10.9
Median Change From Baseline In VLDL Particles Month 6	-4.70 nmol/L Interval -34.5 to 9.5	—
Median Change From Baseline In VLDL Particles Month 12	-6.20 nmol/L Interval -27.9 to 19.2	—
Median Change From Baseline In VLDL Particles Month 18	-6.80 nmol/L Interval -25.1 to 0.3	—
Median Change From Baseline In VLDL Particles Month 24/EOT	-0.30 nmol/L Interval -16.1 to 12.6	—
Median Change From Baseline In VLDL Particles Last Dose	-6.80 nmol/L Interval -19.0 to 6.2	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Results are reported in grams per liter (g/L).

Outcome measures

Measure	Long-term Safety Extension Phase n=21 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Apolipoprotein A1 (ApoA1) Week 4	—	-0.1000 g/L Interval -0.16 to 0.0
Median Change From Baseline In Apolipoprotein A1 (ApoA1) Week 8/EOT	—	-0.0600 g/L Interval -0.27 to 0.0
Median Change From Baseline In Apolipoprotein A1 (ApoA1) Week 12	—	0.0400 g/L Interval -0.02 to 0.15
Median Change From Baseline In Apolipoprotein A1 (ApoA1) Month 6	-0.1400 g/L Interval -0.21 to 0.07	—
Median Change From Baseline In Apolipoprotein A1 (ApoA1) Month 12	-0.0900 g/L Interval -0.2 to 0.01	—
Median Change From Baseline In Apolipoprotein A1 (ApoA1) Month 18	-0.1000 g/L Interval -0.18 to 0.03	—
Median Change From Baseline In Apolipoprotein A1 (ApoA1) Month 24/EOT	0.0100 g/L Interval -0.06 to 0.07	—
Median Change From Baseline In Apolipoprotein A1 (ApoA1) Last Dose	-0.045 g/L Interval -0.17 to 0.03	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Apolipoprotein B (ApoB) Week 4	—	0.0950 units on a scale Interval -0.03 to 0.12
Median Change From Baseline In Apolipoprotein B (ApoB) Week 8/EOT	—	0.0700 units on a scale Interval 0.0 to 0.12
Median Change From Baseline In Apolipoprotein B (ApoB) Week 12	—	0.0500 units on a scale Interval -0.04 to 0.1
Median Change From Baseline In Apolipoprotein B (ApoB) Month 6	0.0400 units on a scale Interval 0.01 to 0.11	—
Median Change From Baseline In Apolipoprotein B (ApoB) Month 12	0.0400 units on a scale Interval -0.02 to 0.1	—
Median Change From Baseline In Apolipoprotein B (ApoB) Month 18	0.0600 units on a scale Interval 0.04 to 0.17	—
Median Change From Baseline In Apolipoprotein B (ApoB) Month 24/EOT	0.0900 units on a scale Interval 0.03 to 0.15	—
Median Change From Baseline In Apolipoprotein B (ApoB) Last Dose	0.060 units on a scale Interval 0.04 to 0.17	—

SECONDARY outcome

Timeframe: Baseline, Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=25 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In ApoA1/ApoB Ratio Week 12	—	-0.0503 Ratio Interval -0.1856 to 0.1939
Median Change From Baseline In ApoA1/ApoB Ratio Month 6	-0.2174 Ratio Interval -0.3638 to -0.0775	—
Median Change From Baseline In ApoA1/ApoB Ratio Month 12	-0.1659 Ratio Interval -0.4509 to -0.0352	—
Median Change From Baseline In ApoA1/ApoB Ratio Month 18	-0.2860 Ratio Interval -0.3918 to -0.0206	—
Median Change From Baseline In ApoA1/ApoB Ratio Month 24/EOT	-0.1172 Ratio Interval -0.306 to 0.1613	—
Median Change From Baseline In ApoA1/ApoB Ratio Last Dose	-0.291 Ratio Interval -0.39 to 0.015	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=25 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Apolipoprotein E Week 4	—	-0.85 mg/dL Interval -1.8 to 0.2
Median Change From Baseline In Apolipoprotein E Week 8/EOT	—	-0.65 mg/dL Interval -2.1 to 0.3
Median Change From Baseline In Apolipoprotein E Week 12	—	0.50 mg/dL Interval -1.0 to 1.2
Median Change From Baseline In Apolipoprotein E Month 6	-0.30 mg/dL Interval -1.0 to 0.3	—
Median Change From Baseline In Apolipoprotein E Month 12	-0.30 mg/dL Interval -0.8 to 0.5	—
Median Change From Baseline In Apolipoprotein E Month 18	-0.10 mg/dL Interval -0.7 to 0.3	—
Median Change From Baseline In Apolipoprotein E Month 24/EOT	0.00 mg/dL Interval -0.6 to 1.0	—
Median Change From Baseline In Apolipoprotein E Last Dose	0.00 mg/dL Interval -0.7 to 0.5	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Lipoprotein-a Week 4	—	0.0000 umol/L Interval -0.0714 to 0.0
Median Change From Baseline In Lipoprotein-a Week 8/EOT	—	0.0000 umol/L Interval -0.0571 to 0.0
Median Change From Baseline In Lipoprotein-a Week 12	—	0.0000 umol/L Interval -0.0357 to 0.0357
Median Change From Baseline In Lipoprotein-a Month 6	0.0000 umol/L Interval -0.0571 to 0.0357	—
Median Change From Baseline In Lipoprotein-a Month 12	0.0000 umol/L Interval -0.0357 to 0.0357	—
Median Change From Baseline In Lipoprotein-a Month 18	0.0000 umol/L Interval -0.0357 to 0.0	—
Median Change From Baseline In Lipoprotein-a Month 24/EOT	0.0000 umol/L Interval -0.0286 to 0.0107	—
Median Change From Baseline In Lipoprotein-a Last Dose	0.000 umol/L Interval -0.036 to 0.0	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Results are reported in nanomoles/milliliter/hour (nmol/mL/h).

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity Week 4	—	-20.5 nmol/mL/h Interval -74.5 to 21.5
Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity Week 8/EOT	—	-13.5 nmol/mL/h Interval -87.5 to 18.0
Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity Week 12	—	15.5 nmol/mL/h Interval -1.0 to 61.0
Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity Month 6	-47.0 nmol/mL/h Interval -107.0 to 49.0	—
Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity Month 12	46.0 nmol/mL/h Interval -29.0 to 75.0	—
Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity Month 18	-19.0 nmol/mL/h Interval -87.0 to 55.0	—
Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity Month 24/EOT	-56.0 nmol/mL/h Interval -105.0 to -28.0	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Results are reported in picomole/milliliter/minute (pmol/mL/min).

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Cholesteryl Ester Transfer Protein Week 4	—	1.95 pmol/mL/min Interval -0.25 to 3.25
Median Change From Baseline In Cholesteryl Ester Transfer Protein Week 8/EOT	—	0.30 pmol/mL/min Interval -2.7 to 3.2
Median Change From Baseline In Cholesteryl Ester Transfer Protein Week 12	—	4.70 pmol/mL/min Interval 1.8 to 10.1
Median Change From Baseline In Cholesteryl Ester Transfer Protein Month 6	1.20 pmol/mL/min Interval -1.4 to 4.4	—
Median Change From Baseline In Cholesteryl Ester Transfer Protein Month 12	-0.60 pmol/mL/min Interval -2.7 to 2.5	—
Median Change From Baseline In Cholesteryl Ester Transfer Protein Month 18	0.50 pmol/mL/min Interval -1.0 to 4.5	—
Median Change From Baseline In Cholesteryl Ester Transfer Protein Month 24/EOT	0.40 pmol/mL/min Interval -3.7 to 4.7	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Results are reported in microgram/milliliter (ug/mL).

Outcome measures

Measure	Long-term Safety Extension Phase n=18 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Prebeta-1 HDL Concentration Week 4	—	1.55 ug/mL Interval -11.5 to 11.45
Median Change From Baseline In Prebeta-1 HDL Concentration Week 8	—	7.55 ug/mL Interval -7.35 to 58.85
Median Change From Baseline In Prebeta-1 HDL Concentration Month 6	-6.90 ug/mL Interval -22.0 to 9.0	—
Median Change From Baseline In Prebeta-1 HDL Concentration Month 12	-10.05 ug/mL Interval -31.95 to 5.37	—
Median Change From Baseline In Prebeta-1 HDL Concentration Month 18	1.94 ug/mL Interval -6.8 to 4.3	—
Median Change From Baseline In Prebeta-1 HDL Concentration Month 24/EOT	-1.35 ug/mL Interval -5.9 to 3.07	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Results are reported as a percentage of cholesterol.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=25 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Macrophage Cholesterol Efflux Week 4	—	-0.800 percentage of cholesterol Interval -2.465 to 0.12
Median Change From Baseline In Macrophage Cholesterol Efflux Week 8	—	-0.705 percentage of cholesterol Interval -1.24 to 0.35
Median Change From Baseline In Macrophage Cholesterol Efflux Month 6	-1.745 percentage of cholesterol Interval -3.17 to -0.14	—
Median Change From Baseline In Macrophage Cholesterol Efflux Month 12	-1.940 percentage of cholesterol Interval -3.11 to 0.16	—
Median Change From Baseline In Macrophage Cholesterol Efflux Month 18	-2.450 percentage of cholesterol Interval -3.5 to -0.68	—
Median Change From Baseline In Macrophage Cholesterol Efflux Month 24/EOT	-0.770 percentage of cholesterol Interval -2.61 to 0.58	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=23 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In C-reactive Protein Week 4	—	0.0000 nmol/L Interval 0.0 to 12.3812
Median Change From Baseline In C-reactive Protein Week 8/EOT	—	0.0000 nmol/L Interval -9.534 to 4.762
Median Change From Baseline In C-reactive Protein Week 12	—	11.4288 nmol/L Interval 0.0 to 28.572
Median Change From Baseline In C-reactive Protein Month 6	0.00 nmol/L Interval -4.76 to 0.0	—
Median Change From Baseline In C-reactive Protein Month 12	0.00 nmol/L Interval -4.76 to 0.0	—
Median Change From Baseline In C-reactive Protein Month 18	0.00 nmol/L Interval -4.76 to 0.0	—
Median Change From Baseline In C-reactive Protein Month 24/EOT	0.00 nmol/L Interval 0.0 to 0.0	—

SECONDARY outcome

Timeframe: Baseline, Week 12, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Results are reported in picograms/milliliter (pg/mL).

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=25 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Glycoprotein A Week 12	—	12.0 pg/mL Interval -6.0 to 36.0
Median Change From Baseline In Glycoprotein A Month 6	-27.0 pg/mL Interval -54.0 to 15.0	—
Median Change From Baseline In Glycoprotein A Month 12	-13.0 pg/mL Interval -61.0 to 10.0	—
Median Change From Baseline In Glycoprotein A Month 18	-26.0 pg/mL Interval -41.0 to 19.0	—
Median Change From Baseline In Glycoprotein A Month 24/EOT	10.0 pg/mL Interval -10.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat population, comprised of all enrolled participants who received at least 1 dose of OCA, was used for all efficacy and safety endpoints. The overall number of the participants is the total number of participants who had at least 1 lab measurement at any given timepoint, including the baseline. The number of participants at a given week may be smaller than the overall number of participants, because some patients may have no follow up measurement at that week, or no baseline.

Outcome measures

Measure	Long-term Safety Extension Phase n=20 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=25 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Fibroblast Growth Factor-19 Week 4	—	81.8800 pg/mL Interval -25.529 to 316.065
Median Change From Baseline In Fibroblast Growth Factor-19 Week 8/EOT	—	112.5460 pg/mL Interval 36.531 to 226.171
Median Change From Baseline In Fibroblast Growth Factor-19 Week 12	—	16.8400 pg/mL Interval -35.498 to 30.692
Median Change From Baseline In Fibroblast Growth Factor-19 Month 6	81.390 pg/mL Interval -6.6 to 201.0	—
Median Change From Baseline In Fibroblast Growth Factor-19 Month 12	29.220 pg/mL Interval -49.19 to 144.35	—
Median Change From Baseline In Fibroblast Growth Factor-19 Month 18	55.230 pg/mL Interval 4.32 to 127.29	—
Median Change From Baseline In Fibroblast Growth Factor-19 Month 24/EOT	-0.740 pg/mL Interval -53.77 to 22.91	—

SECONDARY outcome

Timeframe: Week 12 and Last Dose

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Lipoprotein samples were assessed using nuclear magnetic resonance spectroscopy for the presence/absence of Lipoprotein X. Lipoprotein X sometimes appears with advanced cholestasis and can confound assessment of other lipoprotein concentrations, particularly LDL.

Outcome measures

Measure	Long-term Safety Extension Phase n=21 Participants Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=26 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Participants With Lipoprotein X Week 12	0 Participants	1 Participants
Participants With Lipoprotein X Last Dose	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Results are reported in units/Liter (U/L).

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Alkaline Phosphatase Month 6	—	-43.40 U/L Interval -87.1 to -13.1
Median Change From Baseline In Alkaline Phosphatase Month 12	—	-31.50 U/L Interval -69.9 to -6.7
Median Change From Baseline In Alkaline Phosphatase Month 18	—	-31.90 U/L Interval -47.2 to 1.7
Median Change From Baseline In Alkaline Phosphatase Month 24/EOT	—	6.40 U/L Interval -28.75 to 38.05

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Gamma-glutamyl Transferase Month 6	—	-59.40 U/L Interval -80.9 to -21.3
Median Change From Baseline In Gamma-glutamyl Transferase Month 12	—	-41.60 U/L Interval -92.3 to -28.3
Median Change From Baseline In Gamma-glutamyl Transferase Month 18	—	-40.80 U/L Interval -90.8 to -27.7
Median Change From Baseline In Gamma-glutamyl Transferase Month 24/EOT	—	-30.05 U/L Interval -49.5 to 6.35

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Alanine Aminotransferase Month 6	—	-9.80 U/L Interval -15.9 to -3.6
Median Change From Baseline In Alanine Aminotransferase Month 12	—	-9.80 U/L Interval -16.2 to -1.0
Median Change From Baseline In Alanine Aminotransferase Month 18	—	-11.80 U/L Interval -25.0 to -3.4
Median Change From Baseline In Alanine Aminotransferase Month 24/EOT	—	-5.95 U/L Interval -14.85 to 7.95

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Aspartate Aminotransferase Month 6	—	-5.30 U/L Interval -15.0 to -1.4
Median Change From Baseline In Aspartate Aminotransferase Month 12	—	-3.60 U/L Interval -8.2 to 1.6
Median Change From Baseline In Aspartate Aminotransferase Month 18	—	-6.00 U/L Interval -18.6 to -1.7
Median Change From Baseline In Aspartate Aminotransferase Month 24/EOT	—	-4.50 U/L Interval -13.5 to 4.0

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin Month 6	—	0.0000 umol/L Interval 0.0 to 0.0
Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin Month 12	—	0.0000 umol/L Interval 0.0 to 0.0
Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin Month 18	—	0.0000 umol/L Interval 0.0 to 0.0
Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin Month 24/EOT	—	0.0000 umol/L Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Albumin Month 6	—	-0.60 g/L Interval -1.8 to 3.2
Median Change From Baseline In Albumin Month 12	—	-0.20 g/L Interval -2.1 to 3.2
Median Change From Baseline In Albumin Month 18	—	1.30 g/L Interval 0.3 to 4.3
Median Change From Baseline In Albumin Month 24/EOT	—	0.05 g/L Interval -1.4 to 3.75

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Results are reported in seconds (sec).

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Prothrombin Time Month 6	—	0.000 sec Interval -0.5 to 0.9
Median Change From Baseline In Prothrombin Time Month 12	—	-0.050 sec Interval -0.6 to 0.4
Median Change From Baseline In Prothrombin Time Month 18	—	0.400 sec Interval 0.1 to 0.8
Median Change From Baseline In Prothrombin Time Month 24/EOT	—	0.200 sec Interval -0.2 to 0.75

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Prothrombin International Normalized Ratio Month 6	—	0.0000 ratio Interval 0.0 to 0.1
Median Change From Baseline In Prothrombin International Normalized Ratio Month 12	—	0.0000 ratio Interval 0.0 to 0.0
Median Change From Baseline In Prothrombin International Normalized Ratio Month 18	—	0.0000 ratio Interval 0.0 to 0.1
Median Change From Baseline In Prothrombin International Normalized Ratio Month 24/EOT	—	0.0000 ratio Interval 0.0 to 0.05

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Change in ELF was calculated as ELF score at the end of the study minus ELF score prior to the intervention (at baseline). A decrease in the ELF score was considered good as it reflected a decrease in liver fibrosis, and an increase in ELF score was considered bad as it reflected an increase in liver fibrosis.

Change in ELF scores ranged from -0.56 (good) to + 0.68 (bad).

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Enhanced Liver Fibrosis (ELF) Score Month 12	—	0.000 score on a scale Interval -0.3 to 0.5
Median Change From Baseline In Enhanced Liver Fibrosis (ELF) Score Week 24/EOT	—	0.150 score on a scale Interval -0.05 to 0.55

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Hyaluronic Acid Month 12	—	-5.700 ng/mL Interval -21.02 to 15.77
Median Change From Baseline In Hyaluronic Acid Month 24/EOT	—	-1.805 ng/mL Interval -16.665 to 17.83

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Results are reported in micrograms/Liter (ug/L).

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Amino-terminal Propeptide Of Type III Procollagen Month 12	—	0.670 ug/L Interval -0.22 to 1.2
Median Change From Baseline In Amino-terminal Propeptide Of Type III Procollagen Month 24/EOT	—	2.095 ug/L Interval 1.01 to 3.31

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Tissue Inhibitor Of Metalloproteinases 1 Month 12	—	9.600 ug/L Interval -15.7 to 16.6
Median Change From Baseline In Tissue Inhibitor Of Metalloproteinases 1 Month 24/EOT	—	2.000 ug/L Interval -14.3 to 23.65

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24/EOT

Population: Intent-to-treat was comprised of all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population. The number of participants analyzed includes the subjects who were available at the specific time point of analysis.

Results are reported in kilopascal (kPa).

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=10 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Hepatic Stiffness Month 12	—	-1.15 kPa Interval -9.6 to 0.4
Median Change From Baseline In Hepatic Stiffness Month 24/EOT	—	-1.70 kPa Interval -4.2 to -0.9

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total Bile Acids Month 6	—	-1.56 umol/L Interval -5.23 to 2.58
Median Change From Baseline In Total Bile Acids Month 12	—	-1.14 umol/L Interval -8.94 to 2.88
Median Change From Baseline In Total Bile Acids Month 18	—	-4.61 umol/L Interval -9.21 to 2.8
Median Change From Baseline In Total Bile Acids Month 24/EOT	—	-4.91 umol/L Interval -9.81 to 1.1

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total Endogenous Bile Acid Month 6	—	-0.83 umol/L Interval -3.17 to -0.09
Median Change From Baseline In Total Endogenous Bile Acid Month 12	—	-0.77 umol/L Interval -3.54 to 0.18
Median Change From Baseline In Total Endogenous Bile Acid Month 18	—	-2.19 umol/L Interval -4.62 to -0.48
Median Change From Baseline In Total Endogenous Bile Acid Month 24/EOT	—	-2.02 umol/L Interval -4.22 to 0.98

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total UDCA Month 6	—	-0.34 umol/L Interval -2.67 to 3.47
Median Change From Baseline In Total UDCA Month 12	—	-0.47 umol/L Interval -4.19 to 2.69
Median Change From Baseline In Total UDCA Month 18	—	-2.89 umol/L Interval -4.95 to 2.5
Median Change From Baseline In Total UDCA Month 24/EOT	—	-1.68 umol/L Interval -6.17 to 0.5

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total Chenodeoxycholic Acid Month 6	—	-0.20 umol/L Interval -0.85 to 0.07
Median Change From Baseline In Total Chenodeoxycholic Acid Month 12	—	-0.35 umol/L Interval -1.69 to 0.1
Median Change From Baseline In Total Chenodeoxycholic Acid Month 18	—	-1.28 umol/L Interval -1.84 to -0.06
Median Change From Baseline In Total Chenodeoxycholic Acid Month 24/EOT	—	-1.17 umol/L Interval -1.76 to 0.33

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total Lithocholic Acid Month 6	—	0.00 umol/L Interval -0.03 to 0.11
Median Change From Baseline In Total Lithocholic Acid Month 12	—	0.00 umol/L Interval -0.05 to 0.06
Median Change From Baseline In Total Lithocholic Acid Month 18	—	0.00 umol/L Interval -0.1 to 0.0
Median Change From Baseline In Total Lithocholic Acid Month 24/EOT	—	0.00 umol/L Interval -0.19 to 0.0

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total Cholic Acid Month 6	—	-0.39 umol/L Interval -1.39 to 0.0
Median Change From Baseline In Total Cholic Acid Month 12	—	-0.48 umol/L Interval -1.44 to 0.0
Median Change From Baseline In Total Cholic Acid Month 18	—	-0.49 umol/L Interval -1.49 to -0.09
Median Change From Baseline In Total Cholic Acid Month 24/EOT	—	-0.39 umol/L Interval -1.18 to -0.04

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Median Change From Baseline In Total Deoxycholic Acid Month 6	—	-0.59 umol/L Interval -0.89 to -0.04
Median Change From Baseline In Total Deoxycholic Acid Month 12	—	-0.56 umol/L Interval -1.14 to 0.01
Median Change From Baseline In Total Deoxycholic Acid Month 18	—	-0.51 umol/L Interval -1.21 to -0.27
Median Change From Baseline In Total Deoxycholic Acid Month 24/EOT	—	-0.59 umol/L Interval -1.1 to 0.32

SECONDARY outcome

Timeframe: Baseline, Month 24/EOT

Population: Intent-to-treat was comprised of all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population. The number of participants analyzed includes the subjects who were available at the specific time point of analysis.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=17 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Absolute Change From Baseline In HDL Cholesterol Concentration	—	0.5 mmol/L Interval -4.6 to 5.5

SECONDARY outcome

Timeframe: Baseline, Month 24/EOT

Population: Intent-to-treat was comprised of all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population. The number of participants analyzed includes the subjects who were available at the specific time point of analysis.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=17 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Absolute Change From Baseline In HDL Particle Size	—	0.04 nm Interval -0.1 to 0.19

SECONDARY outcome

Timeframe: Baseline, Month 24/EOT

Population: Intent-to-treat: all enrolled participants who received at least 1 dose of OCA during the study. All efficacy and safety endpoints were analyzed using the intent-to-treat population.

Outcome measures

Measure	Long-term Safety Extension Phase Participants received OCA 10 mg QD for up to 2 years.	Primary Treatment Phase n=20 Participants All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.
Absolute Change From Baseline In HDL Particle Number	—	-0.09 umol/L Interval -1.78 to 1.59

Adverse Events

Primary Treatment Phase

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Long-term Safety Extension Phase

Serious events: 5 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Primary Treatment Phase n=26 participants at risk All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.	Long-term Safety Extension Phase n=21 participants at risk Participants received OCA 10 mg QD for up to 2 years.
Gastrointestinal disorders Ascites	3.8% 1/26 • Number of events 1 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	0.00% 0/21 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Hepatobiliary disorders Jaundice	3.8% 1/26 • Number of events 1 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	0.00% 0/21 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Cardiac disorders Stress cardiomyopathy	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	4.8% 1/21 • Number of events 1 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	4.8% 1/21 • Number of events 1 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Infections and infestations Pneumonia	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	4.8% 1/21 • Number of events 1 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Infections and infestations Sepsis	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	4.8% 1/21 • Number of events 1 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Psychiatric disorders Depression	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	4.8% 1/21 • Number of events 1 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Vascular disorders Aortic aneurysm	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	4.8% 1/21 • Number of events 1 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.

Other adverse events

Measure	Primary Treatment Phase n=26 participants at risk All participants were treated with OCA (oral administration, 10 mg QD) for 8 weeks and continued their prestudy dose of UDCA. After completion of the 8-week PTP of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter the open-label LTSE phase, during which they could receive 10 mg OCA QD for up to 2 years.	Long-term Safety Extension Phase n=21 participants at risk Participants received OCA 10 mg QD for up to 2 years.
Skin and subcutaneous tissue disorders Pruritus	50.0% 13/26 • Number of events 17 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	28.6% 6/21 • Number of events 13 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
General disorders Fatigue	15.4% 4/26 • Number of events 4 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	0.00% 0/21 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
General disorders Oedema peripheral	7.7% 2/26 • Number of events 3 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	0.00% 0/21 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
General disorders Pyrexia	7.7% 2/26 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	0.00% 0/21 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Gastrointestinal disorders Diarrhoea	7.7% 2/26 • Number of events 4 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 3 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Gastrointestinal disorders Constipation	7.7% 2/26 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	0.00% 0/21 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Gastrointestinal disorders Nausea	7.7% 2/26 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Nervous system disorders Dizziness	11.5% 3/26 • Number of events 3 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Nervous system disorders Headache	7.7% 2/26 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	0.00% 0/21 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Infections and infestations Sinusitis	7.7% 2/26 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	14.3% 3/21 • Number of events 3 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Musculoskeletal and connective tissue disorders Back pain	7.7% 2/26 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	0.00% 0/21 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	14.3% 3/21 • Number of events 3 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Investigations Blood alkaline phosphatase increased	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Investigations Low density lipoprotein increased	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Infections and infestations Bronchitis	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Infections and infestations Tooth abscess	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
General disorders Chills	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
General disorders Influenza like illness	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Gastrointestinal disorders Abdominal pain	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Gastrointestinal disorders Hiatus hernia	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	14.3% 3/21 • Number of events 3 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Eye disorders Dry eye	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.
Cardiac disorders Coronary artery disease	0.00% 0/26 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.	9.5% 2/21 • Number of events 2 • Adverse event data were collected from the time of the first dose of investigational product until the participant fully completed participation in the study, up to 2 years.

Additional Information

Medical Information

Intercept Pharmaceuticals, Inc.

Phone: +1 844-782-4278

Email: medinfo@interceptpharma.com

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