Primary Biliary Cirrhosis
Conditions
Brief summary
The purpose of this study was to determine if OCA had an effect on cholesterol levels in the blood in participants with primary biliary cirrhosis (PBC).
Detailed description
This was a phase 2, open-label, multicenter study evaluating the effects of OCA on lipoprotein metabolism in participants with PBC; in particular, OCA's effects on high-density lipoprotein cholesterol. Nuclear magnetic resonance spectroscopy was utilized to quantify the changes in lipoprotein particle sizes and concentrations. Components of reverse cholesterol transport were also assessed.
Interventions
DRUGObeticholic Acid
All participants were treated with OCA (oral administration, 10 mg, once daily \[QD\]) for 8 weeks and continued their prestudy dose of ursodeoxycholic acid (UDCA). After completion of the 8-week Primary Treatment Phase 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 an open-label, long-term safety extension phase, during which they could receive 10 mg OCA QD for up to 2 years.
Sponsors
Intercept Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Definite or probable PBC diagnosis as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors: * History of elevated alkaline phosphatase levels for at least 6 months * A positive anti-microbial antibody (AMA) titer or, if AMA negative or in low titer (\<1:80), PBC-specific antibodies * Liver biopsy consistent with PBC 2. Taking UDCA for at least 12 months (stable dose for ≥ 3 months) prior to Day 0 or unable to tolerate UDCA (no UDCA for ≥ 3 months prior to Day 0). 3. Contraception: Female participants must have been postmenopausal, surgically sterile, or if premenopausal, were prepared to use ≥ 1 effective (≤ 1% failure rate) method of contraception during the trial and until at least 30 days after the last dose of Investigational Product. 4. Must have provided written informed consent and agreed to comply with the trial protocol. Key
Exclusion criteria
1. Participants with decompensated PBC (as determined by the Investigator). 2. Severe pruritus or systemic treatment for pruritus (for example, treatment with bile acid sequestrants or rifampicin) within 2 months of Day 0. 3. History or presence of other significant liver diseases including: * Active or chronic Hepatitis B or C virus infection * Primary sclerosing cholangitis * Alcoholic liver disease * Definite autoimmune liver disease or overlap hepatitis * Nonalcoholic steatohepatitis Note: Participants with Gilbert's disease or those with a history of hepatitis B who were currently antigen negative and seroconverted were not considered exclusionary. 4. Uncontrolled diabetes or other uncontrolled or unstable medical condition that may have interfered with trial results. 5. Administration of any of the following medications as specified below: * Prohibited 28 days prior to Day 0: bile acid sequestrants including cholestyramine, colesevelam, colestipol or omega-3 fatty acid containing dietary supplements * Prohibited 3 months prior to Day 0 and throughout trial participation: serum-lipid modifying agents including 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, fenofibrate or other fibrates, nicotinic acid and derivatives, ezetimibe, Vitamin E (other than as standard dietary supplement) * Prohibited 6 months prior to Day 0 and throughout the trial participation: azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin) * Prohibited 12 months prior to Day 0 and throughout the trial participation: antibodies or immunotherapy directed against interleukins or other cytokines or chemokines 6. Planned change in diet or exercise habits during participation in the trial. 7. Presence or history of clinically significant cardiac arrhythmias that may have prohibited the participant from participating in the trial. 8. If female: known pregnancy, or had a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating. 9. Recent (3 months prior to day 0) participation in another trial involving OCA or participation in another investigational trial (30 days prior to Day 0) and during the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute Change From Baseline In High-density Lipoprotein (HDL) Cholesterol Concentration | Baseline, Week 8 |
| Absolute Change From Baseline In HDL Particle Size | Baseline, Week 8 |
| Absolute Change From Baseline In HDL Particle Number | Baseline, Week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Change From Baseline In Total Lithocholic Acid | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Area Under The Concentration-time Curve From Hour 0 To Last Sampling Time (Hour 6) (AUC0-6) For OCA And Conjugates | Week 8 | Results are reported in hour\*nanograms per milliliter (h\*ng/mL). |
| Median Change From Baseline In Total Cholesterol | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In Total Triglycerides | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In Total Cholic Acid | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In LDL Particle Size | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In Total Deoxycholic Acid | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Absolute Change From Baseline In HDL Cholesterol Concentration | Baseline, Month 24/EOT | — |
| Median Change From Baseline In Total LDL Particles | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | Results are reported in nanomoles per liter (nmol/L). |
| Median Change From Baseline In HDL Particle Number At Weeks 4, 8, and 12 | Baseline, Week 4, Week 8, Week 12 | — |
| Median Change From Week 8 In HDL Cholesterol Concentration At Week 12 | Week 8, Week 12 | — |
| Median Change From Week 8 In HDL Particle Size At Week 12 | Week 8, Week 12 | — |
| Median Change From Week 8 In HDL Particle Number At Week 12 | Week 8, Week 12 | — |
| Maximum Plasma Concentration (Cmax) Of OCA And Conjugates | Week 8 | Results are reported in nanograms per milliliter (ng/mL). |
| Median Change From Baseline In HDL Cholesterol Concentration At Weeks 4, 8, and 12 | Baseline, Week 4, Week 8, Week 12 | — |
| Median Change From Baseline In HDL Particle Size At Weeks 4, 8, and 12 | Baseline, Week 4, Week 8, Week 12 | — |
| Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol | Baseline, Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | Results are reported in milligrams per deciliter (mg/dL). |
| Median Change From Baseline In VLDL Particle Size | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In VLDL Particles | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | Results are reported in grams per liter (g/L). |
| Median Change From Baseline In Apolipoprotein B (ApoB) | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In ApoA1/ApoB Ratio | Baseline, Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In Apolipoprotein E | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In Lipoprotein-a | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT, Last Dose | — |
| Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT | Results are reported in nanomoles/milliliter/hour (nmol/mL/h). |
| Median Change From Baseline In Cholesteryl Ester Transfer Protein | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT | Results are reported in picomole/milliliter/minute (pmol/mL/min). |
| Median Change From Baseline In Prebeta-1 HDL Concentration | Baseline, Week 4, Week 8/End of Treatment (EOT), Month 6, Month 12, Month 18, Month 24/EOT | Results are reported in microgram/milliliter (ug/mL). |
| Median Change From Baseline In Macrophage Cholesterol Efflux | Baseline, Week 4, Week 8/End of Treatment (EOT), Month 6, Month 12, Month 18, Month 24/EOT | Results are reported as a percentage of cholesterol. |
| Median Change From Baseline In C-reactive Protein | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Glycoprotein A | Baseline, Week 12, Month 6, Month 12, Month 18, Month 24/EOT | Results are reported in picograms/milliliter (pg/mL). |
| Median Change From Baseline In Fibroblast Growth Factor-19 | Baseline, Week 4, Week 8/End of Treatment (EOT), Week 12, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Participants With Lipoprotein X | Week 12 and Last Dose | 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. |
| Median Change From Baseline In Alkaline Phosphatase | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | Results are reported in units/Liter (U/L). |
| Median Change From Baseline In Gamma-glutamyl Transferase | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Alanine Aminotransferase | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Aspartate Aminotransferase | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Albumin | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Prothrombin Time | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | Results are reported in seconds (sec). |
| Median Change From Baseline In Prothrombin International Normalized Ratio | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Enhanced Liver Fibrosis (ELF) Score | Baseline, Month 12, Month 24/EOT | 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). |
| Median Change From Baseline In Hyaluronic Acid | Baseline, Month 12, Month 24/EOT | — |
| Median Change From Baseline In Amino-terminal Propeptide Of Type III Procollagen | Baseline, Month 12, Month 24/EOT | Results are reported in micrograms/Liter (ug/L). |
| Median Change From Baseline In Tissue Inhibitor Of Metalloproteinases 1 | Baseline, Month 12, Month 24/EOT | — |
| Absolute Change From Baseline In HDL Particle Number | Baseline, Month 24/EOT | — |
| Median Change From Baseline In Total Bile Acids | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Total Endogenous Bile Acid | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Median Change From Baseline In Total UDCA | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
| Absolute Change From Baseline In HDL Particle Size | Baseline, Month 24/EOT | — |
| Median Change From Baseline In Hepatic Stiffness | Baseline, Month 12, Month 24/EOT | Results are reported in kilopascal (kPa). |
| Time To Reach Cmax (Tmax) For OCA And Conjugates | Week 8 | Results are reported in hours (h). |
| Median Change From Baseline In Total Chenodeoxycholic Acid | Baseline, Month 6, Month 12, Month 18, Month 24/EOT | — |
Countries
United States
Participant flow
Recruitment details
Recruitment started 19-Nov-2013 and completed 16-May-2014 in the primary treatment phase (PTP). Thirty-three participants were screened and 27 enrolled.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Obeticholic Acid 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. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Long-term Safety Extension Phase | Participant Unavailable for Final Study Visit | 0 | 1 |
| Long-term Safety Extension Phase | Physician Decision | 0 | 1 |
| Long-term Safety Extension Phase | Pruritus | 0 | 3 |
| Long-term Safety Extension Phase | Withdrawal by Subject | 0 | 1 |
| Primary Treatment Phase | Adverse Event | 2 | 0 |
Baseline characteristics
| Characteristic | Obeticholic Acid |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 56.5 years STANDARD_DEVIATION 9.15 |
| HDL Particle Concentration (total) | 30.08 µmol/L STANDARD_DEVIATION 7.228 |
| HDL Particle Size | 10.19 nm STANDARD_DEVIATION 0.734 |
| High-density Lipoprotein (HDL) Cholesterol Concentration | 1.86 mmol/L STANDARD_DEVIATION 0.51798 |
| Race/Ethnicity, Customized Non-White/Hispanic | 1 participants |
| Race/Ethnicity, Customized White | 25 participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 21 |
| other Total, other adverse events | 18 / 26 | 17 / 21 |
| serious Total, serious adverse events | 1 / 26 | 5 / 21 |
Outcome results
Primary
Absolute Change From Baseline In HDL Particle Number
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Primary Treatment Phase | Absolute Change From Baseline In HDL Particle Number | -0.06 umol/L |
95% CI: [-1.58, 1.46]
Primary
Absolute Change From Baseline In HDL Particle Size
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Primary Treatment Phase | Absolute Change From Baseline In HDL Particle Size | -0.44 nm |
95% CI: [-0.63, -0.25]
Primary
Absolute Change From Baseline In High-density Lipoprotein (HDL) Cholesterol Concentration
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Primary Treatment Phase | Absolute Change From Baseline In High-density Lipoprotein (HDL) Cholesterol Concentration | -0.38 mmol/L |
95% CI: [-0.51, -0.24]
Secondary
Absolute Change From Baseline In HDL Cholesterol Concentration
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Primary Treatment Phase | Absolute Change From Baseline In HDL Cholesterol Concentration | 0.5 mmol/L |
p-value: 0.852ANCOVA
Secondary
Absolute Change From Baseline In HDL Particle Number
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Primary Treatment Phase | Absolute Change From Baseline In HDL Particle Number | -0.09 umol/L |
p-value: 0.912ANCOVA
Secondary
Absolute Change From Baseline In HDL Particle Size
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Primary Treatment Phase | Absolute Change From Baseline In HDL Particle Size | 0.04 nm |
p-value: 0.549ANCOVA
Secondary
Area Under The Concentration-time Curve From Hour 0 To Last Sampling Time (Hour 6) (AUC0-6) For OCA And Conjugates
Results are reported in hour\*nanograms per milliliter (h\*ng/mL).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Primary Treatment Phase | 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 |
| Primary Treatment Phase | 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 |
| Primary Treatment Phase | 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 |
| Primary Treatment Phase | 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
Maximum Plasma Concentration (Cmax) Of OCA And Conjugates
Results are reported in nanograms per milliliter (ng/mL).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Primary Treatment Phase | Maximum Plasma Concentration (Cmax) Of OCA And Conjugates | OCA | 107 ng/mL | Standard Deviation 112 |
| Primary Treatment Phase | Maximum Plasma Concentration (Cmax) Of OCA And Conjugates | Glycine Conjugate (Glyco)-OCA | 212 ng/mL | Standard Deviation 144 |
| Primary Treatment Phase | Maximum Plasma Concentration (Cmax) Of OCA And Conjugates | Taurine Conjugate (Tauro)-OCA | 219 ng/mL | Standard Deviation 208 |
| Primary Treatment Phase | Maximum Plasma Concentration (Cmax) Of OCA And Conjugates | Total-OCA | 409 ng/mL | Standard Deviation 299 |
Secondary
Median Change From Baseline In Alanine Aminotransferase
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Alanine Aminotransferase | Month 6 | -9.80 U/L |
| Primary Treatment Phase | Median Change From Baseline In Alanine Aminotransferase | Month 12 | -9.80 U/L |
| Primary Treatment Phase | Median Change From Baseline In Alanine Aminotransferase | Month 18 | -11.80 U/L |
| Primary Treatment Phase | Median Change From Baseline In Alanine Aminotransferase | Month 24/EOT | -5.95 U/L |
Secondary
Median Change From Baseline In Albumin
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Albumin | Month 6 | -0.60 g/L |
| Primary Treatment Phase | Median Change From Baseline In Albumin | Month 12 | -0.20 g/L |
| Primary Treatment Phase | Median Change From Baseline In Albumin | Month 18 | 1.30 g/L |
| Primary Treatment Phase | Median Change From Baseline In Albumin | Month 24/EOT | 0.05 g/L |
Secondary
Median Change From Baseline In Alkaline Phosphatase
Results are reported in units/Liter (U/L).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Alkaline Phosphatase | Month 6 | -43.40 U/L |
| Primary Treatment Phase | Median Change From Baseline In Alkaline Phosphatase | Month 12 | -31.50 U/L |
| Primary Treatment Phase | Median Change From Baseline In Alkaline Phosphatase | Month 18 | -31.90 U/L |
| Primary Treatment Phase | Median Change From Baseline In Alkaline Phosphatase | Month 24/EOT | 6.40 U/L |
Secondary
Median Change From Baseline In Amino-terminal Propeptide Of Type III Procollagen
Results are reported in micrograms/Liter (ug/L).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Amino-terminal Propeptide Of Type III Procollagen | Month 12 | 0.670 ug/L |
| Primary Treatment Phase | Median Change From Baseline In Amino-terminal Propeptide Of Type III Procollagen | Month 24/EOT | 2.095 ug/L |
Secondary
Median Change From Baseline In ApoA1/ApoB Ratio
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In ApoA1/ApoB Ratio | Week 12 | -0.0503 Ratio |
| Long-term Safety Extension Phase | Median Change From Baseline In ApoA1/ApoB Ratio | Month 6 | -0.2174 Ratio |
| Long-term Safety Extension Phase | Median Change From Baseline In ApoA1/ApoB Ratio | Month 12 | -0.1659 Ratio |
| Long-term Safety Extension Phase | Median Change From Baseline In ApoA1/ApoB Ratio | Month 18 | -0.2860 Ratio |
| Long-term Safety Extension Phase | Median Change From Baseline In ApoA1/ApoB Ratio | Month 24/EOT | -0.1172 Ratio |
| Long-term Safety Extension Phase | Median Change From Baseline In ApoA1/ApoB Ratio | Last Dose | -0.291 Ratio |
Secondary
Median Change From Baseline In Apolipoprotein A1 (ApoA1)
Results are reported in grams per liter (g/L).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Week 4 | -0.1000 g/L |
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Week 8/EOT | -0.0600 g/L |
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Week 12 | 0.0400 g/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Month 6 | -0.1400 g/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Month 12 | -0.0900 g/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Month 18 | -0.1000 g/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Month 24/EOT | 0.0100 g/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein A1 (ApoA1) | Last Dose | -0.045 g/L |
Secondary
Median Change From Baseline In Apolipoprotein B (ApoB)
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein B (ApoB) | Week 4 | 0.0950 units on a scale |
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein B (ApoB) | Week 8/EOT | 0.0700 units on a scale |
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein B (ApoB) | Week 12 | 0.0500 units on a scale |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein B (ApoB) | Month 6 | 0.0400 units on a scale |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein B (ApoB) | Month 12 | 0.0400 units on a scale |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein B (ApoB) | Month 18 | 0.0600 units on a scale |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein B (ApoB) | Month 24/EOT | 0.0900 units on a scale |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein B (ApoB) | Last Dose | 0.060 units on a scale |
Secondary
Median Change From Baseline In Apolipoprotein E
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein E | Week 4 | -0.85 mg/dL |
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein E | Week 8/EOT | -0.65 mg/dL |
| Primary Treatment Phase | Median Change From Baseline In Apolipoprotein E | Week 12 | 0.50 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein E | Month 6 | -0.30 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein E | Month 12 | -0.30 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein E | Month 18 | -0.10 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein E | Month 24/EOT | 0.00 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Apolipoprotein E | Last Dose | 0.00 mg/dL |
Secondary
Median Change From Baseline In Aspartate Aminotransferase
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Aspartate Aminotransferase | Month 6 | -5.30 U/L |
| Primary Treatment Phase | Median Change From Baseline In Aspartate Aminotransferase | Month 12 | -3.60 U/L |
| Primary Treatment Phase | Median Change From Baseline In Aspartate Aminotransferase | Month 18 | -6.00 U/L |
| Primary Treatment Phase | Median Change From Baseline In Aspartate Aminotransferase | Month 24/EOT | -4.50 U/L |
Secondary
Median Change From Baseline In Cholesteryl Ester Transfer Protein
Results are reported in picomole/milliliter/minute (pmol/mL/min).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Cholesteryl Ester Transfer Protein | Week 4 | 1.95 pmol/mL/min |
| Primary Treatment Phase | Median Change From Baseline In Cholesteryl Ester Transfer Protein | Week 8/EOT | 0.30 pmol/mL/min |
| Primary Treatment Phase | Median Change From Baseline In Cholesteryl Ester Transfer Protein | Week 12 | 4.70 pmol/mL/min |
| Long-term Safety Extension Phase | Median Change From Baseline In Cholesteryl Ester Transfer Protein | Month 6 | 1.20 pmol/mL/min |
| Long-term Safety Extension Phase | Median Change From Baseline In Cholesteryl Ester Transfer Protein | Month 12 | -0.60 pmol/mL/min |
| Long-term Safety Extension Phase | Median Change From Baseline In Cholesteryl Ester Transfer Protein | Month 18 | 0.50 pmol/mL/min |
| Long-term Safety Extension Phase | Median Change From Baseline In Cholesteryl Ester Transfer Protein | Month 24/EOT | 0.40 pmol/mL/min |
Secondary
Median Change From Baseline In C-reactive Protein
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In C-reactive Protein | Week 4 | 0.0000 nmol/L |
| Primary Treatment Phase | Median Change From Baseline In C-reactive Protein | Week 8/EOT | 0.0000 nmol/L |
| Primary Treatment Phase | Median Change From Baseline In C-reactive Protein | Week 12 | 11.4288 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In C-reactive Protein | Month 6 | 0.00 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In C-reactive Protein | Month 12 | 0.00 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In C-reactive Protein | Month 18 | 0.00 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In C-reactive Protein | Month 24/EOT | 0.00 nmol/L |
Secondary
Median Change From Baseline In Enhanced Liver Fibrosis (ELF) Score
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Enhanced Liver Fibrosis (ELF) Score | Month 12 | 0.000 score on a scale |
| Primary Treatment Phase | Median Change From Baseline In Enhanced Liver Fibrosis (ELF) Score | Week 24/EOT | 0.150 score on a scale |
Secondary
Median Change From Baseline In Fibroblast Growth Factor-19
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Fibroblast Growth Factor-19 | Week 4 | 81.8800 pg/mL |
| Primary Treatment Phase | Median Change From Baseline In Fibroblast Growth Factor-19 | Week 8/EOT | 112.5460 pg/mL |
| Primary Treatment Phase | Median Change From Baseline In Fibroblast Growth Factor-19 | Week 12 | 16.8400 pg/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Fibroblast Growth Factor-19 | Month 6 | 81.390 pg/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Fibroblast Growth Factor-19 | Month 12 | 29.220 pg/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Fibroblast Growth Factor-19 | Month 18 | 55.230 pg/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Fibroblast Growth Factor-19 | Month 24/EOT | -0.740 pg/mL |
Secondary
Median Change From Baseline In Gamma-glutamyl Transferase
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Gamma-glutamyl Transferase | Month 6 | -59.40 U/L |
| Primary Treatment Phase | Median Change From Baseline In Gamma-glutamyl Transferase | Month 12 | -41.60 U/L |
| Primary Treatment Phase | Median Change From Baseline In Gamma-glutamyl Transferase | Month 18 | -40.80 U/L |
| Primary Treatment Phase | Median Change From Baseline In Gamma-glutamyl Transferase | Month 24/EOT | -30.05 U/L |
Secondary
Median Change From Baseline In Glycoprotein A
Results are reported in picograms/milliliter (pg/mL).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Glycoprotein A | Week 12 | 12.0 pg/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Glycoprotein A | Month 6 | -27.0 pg/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Glycoprotein A | Month 12 | -13.0 pg/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Glycoprotein A | Month 18 | -26.0 pg/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Glycoprotein A | Month 24/EOT | 10.0 pg/mL |
Secondary
Median Change From Baseline In HDL Cholesterol Concentration At Weeks 4, 8, and 12
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In HDL Cholesterol Concentration At Weeks 4, 8, and 12 | Week 4 | -0.2072 mmol/L |
| Primary Treatment Phase | Median Change From Baseline In HDL Cholesterol Concentration At Weeks 4, 8, and 12 | Week 8 | -0.3108 mmol/L |
| Primary Treatment Phase | Median Change From Baseline In HDL Cholesterol Concentration At Weeks 4, 8, and 12 | Week 12 | 0.0518 mmol/L |
Secondary
Median Change From Baseline In HDL Particle Number At Weeks 4, 8, and 12
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In HDL Particle Number At Weeks 4, 8, and 12 | Week 4 | 0.55 umol/L |
| Primary Treatment Phase | Median Change From Baseline In HDL Particle Number At Weeks 4, 8, and 12 | Week 8 | 0.60 umol/L |
| Primary Treatment Phase | Median Change From Baseline In HDL Particle Number At Weeks 4, 8, and 12 | Week 12 | 1.60 umol/L |
Secondary
Median Change From Baseline In HDL Particle Size At Weeks 4, 8, and 12
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In HDL Particle Size At Weeks 4, 8, and 12 | Week 4 | -0.30 nm |
| Primary Treatment Phase | Median Change From Baseline In HDL Particle Size At Weeks 4, 8, and 12 | Week 8 | -0.30 nm |
| Primary Treatment Phase | Median Change From Baseline In HDL Particle Size At Weeks 4, 8, and 12 | Week 12 | 0.00 nm |
Secondary
Median Change From Baseline In Hepatic Stiffness
Results are reported in kilopascal (kPa).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Hepatic Stiffness | Month 12 | -1.15 kPa |
| Primary Treatment Phase | Median Change From Baseline In Hepatic Stiffness | Month 24/EOT | -1.70 kPa |
Secondary
Median Change From Baseline In Hyaluronic Acid
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Hyaluronic Acid | Month 12 | -5.700 ng/mL |
| Primary Treatment Phase | Median Change From Baseline In Hyaluronic Acid | Month 24/EOT | -1.805 ng/mL |
Secondary
Median Change From Baseline In LDL Particle Size
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In LDL Particle Size | Week 4 | -0.30 nm |
| Primary Treatment Phase | Median Change From Baseline In LDL Particle Size | Week 8/EOT | -0.10 nm |
| Primary Treatment Phase | Median Change From Baseline In LDL Particle Size | Week 12 | 0.00 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In LDL Particle Size | Month 6 | -0.10 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In LDL Particle Size | Month 12 | -0.20 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In LDL Particle Size | Month 18 | -0.10 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In LDL Particle Size | Month 24/EOT | -0.10 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In LDL Particle Size | Last Dose | -0.10 nm |
Secondary
Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity
Results are reported in nanomoles/milliliter/hour (nmol/mL/h).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity | Week 4 | -20.5 nmol/mL/h |
| Primary Treatment Phase | Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity | Week 8/EOT | -13.5 nmol/mL/h |
| Primary Treatment Phase | Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity | Week 12 | 15.5 nmol/mL/h |
| Long-term Safety Extension Phase | Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity | Month 6 | -47.0 nmol/mL/h |
| Long-term Safety Extension Phase | Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity | Month 12 | 46.0 nmol/mL/h |
| Long-term Safety Extension Phase | Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity | Month 18 | -19.0 nmol/mL/h |
| Long-term Safety Extension Phase | Median Change From Baseline In Lecithin-cholesterol Acyltransferase Activity | Month 24/EOT | -56.0 nmol/mL/h |
Secondary
Median Change From Baseline In Lipoprotein-a
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Lipoprotein-a | Week 8/EOT | 0.0000 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Lipoprotein-a | Week 12 | 0.0000 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Lipoprotein-a | Week 4 | 0.0000 umol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Lipoprotein-a | Month 24/EOT | 0.0000 umol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Lipoprotein-a | Month 6 | 0.0000 umol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Lipoprotein-a | Last Dose | 0.000 umol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Lipoprotein-a | Month 12 | 0.0000 umol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Lipoprotein-a | Month 18 | 0.0000 umol/L |
Secondary
Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct)
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Week 8/EOT | 0.31 mmol/L |
| Primary Treatment Phase | Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Week 4 | 0.27 mmol/L |
| Primary Treatment Phase | Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Week 12 | 0.18 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Month 6 | 0.3108 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Month 12 | 0.4403 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Month 18 | 0.5957 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Month 24/EOT | 0.3108 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Low-density Lipoprotein (LDL) Cholesterol (Direct) | Last Dose | 0.518 mmol/L |
Secondary
Median Change From Baseline In Macrophage Cholesterol Efflux
Results are reported as a percentage of cholesterol.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Macrophage Cholesterol Efflux | Week 4 | -0.800 percentage of cholesterol |
| Primary Treatment Phase | Median Change From Baseline In Macrophage Cholesterol Efflux | Week 8 | -0.705 percentage of cholesterol |
| Long-term Safety Extension Phase | Median Change From Baseline In Macrophage Cholesterol Efflux | Month 6 | -1.745 percentage of cholesterol |
| Long-term Safety Extension Phase | Median Change From Baseline In Macrophage Cholesterol Efflux | Month 12 | -1.940 percentage of cholesterol |
| Long-term Safety Extension Phase | Median Change From Baseline In Macrophage Cholesterol Efflux | Month 18 | -2.450 percentage of cholesterol |
| Long-term Safety Extension Phase | Median Change From Baseline In Macrophage Cholesterol Efflux | Month 24/EOT | -0.770 percentage of cholesterol |
Secondary
Median Change From Baseline In Prebeta-1 HDL Concentration
Results are reported in microgram/milliliter (ug/mL).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Prebeta-1 HDL Concentration | Week 4 | 1.55 ug/mL |
| Primary Treatment Phase | Median Change From Baseline In Prebeta-1 HDL Concentration | Week 8 | 7.55 ug/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Prebeta-1 HDL Concentration | Month 6 | -6.90 ug/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Prebeta-1 HDL Concentration | Month 12 | -10.05 ug/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Prebeta-1 HDL Concentration | Month 18 | 1.94 ug/mL |
| Long-term Safety Extension Phase | Median Change From Baseline In Prebeta-1 HDL Concentration | Month 24/EOT | -1.35 ug/mL |
Secondary
Median Change From Baseline In Prothrombin International Normalized Ratio
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Prothrombin International Normalized Ratio | Month 6 | 0.0000 ratio |
| Primary Treatment Phase | Median Change From Baseline In Prothrombin International Normalized Ratio | Month 12 | 0.0000 ratio |
| Primary Treatment Phase | Median Change From Baseline In Prothrombin International Normalized Ratio | Month 18 | 0.0000 ratio |
| Primary Treatment Phase | Median Change From Baseline In Prothrombin International Normalized Ratio | Month 24/EOT | 0.0000 ratio |
Secondary
Median Change From Baseline In Prothrombin Time
Results are reported in seconds (sec).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Prothrombin Time | Month 6 | 0.000 sec |
| Primary Treatment Phase | Median Change From Baseline In Prothrombin Time | Month 12 | -0.050 sec |
| Primary Treatment Phase | Median Change From Baseline In Prothrombin Time | Month 18 | 0.400 sec |
| Primary Treatment Phase | Median Change From Baseline In Prothrombin Time | Month 24/EOT | 0.200 sec |
Secondary
Median Change From Baseline In Tissue Inhibitor Of Metalloproteinases 1
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Tissue Inhibitor Of Metalloproteinases 1 | Month 12 | 9.600 ug/L |
| Primary Treatment Phase | Median Change From Baseline In Tissue Inhibitor Of Metalloproteinases 1 | Month 24/EOT | 2.000 ug/L |
Secondary
Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin | Month 6 | 0.0000 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin | Month 12 | 0.0000 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin | Month 18 | 0.0000 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total And Unconjugated (Direct) Bilirubin | Month 24/EOT | 0.0000 umol/L |
Secondary
Median Change From Baseline In Total Bile Acids
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total Bile Acids | Month 6 | -1.56 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Bile Acids | Month 12 | -1.14 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Bile Acids | Month 18 | -4.61 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Bile Acids | Month 24/EOT | -4.91 umol/L |
Secondary
Median Change From Baseline In Total Chenodeoxycholic Acid
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total Chenodeoxycholic Acid | Month 6 | -0.20 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Chenodeoxycholic Acid | Month 12 | -0.35 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Chenodeoxycholic Acid | Month 18 | -1.28 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Chenodeoxycholic Acid | Month 24/EOT | -1.17 umol/L |
Secondary
Median Change From Baseline In Total Cholesterol
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total Cholesterol | Week 4 | -0.0518 mmol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Cholesterol | Week 8/EOT | -0.2849 mmol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Cholesterol | Week 12 | 0.2331 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Cholesterol | Month 6 | -0.1813 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Cholesterol | Month 12 | 0.0777 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Cholesterol | Month 18 | 0.2849 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Cholesterol | Month 24/EOT | -0.0777 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Cholesterol | Last Dose | 0.285 mmol/L |
Secondary
Median Change From Baseline In Total Cholic Acid
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total Cholic Acid | Month 6 | -0.39 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Cholic Acid | Month 12 | -0.48 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Cholic Acid | Month 18 | -0.49 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Cholic Acid | Month 24/EOT | -0.39 umol/L |
Secondary
Median Change From Baseline In Total Deoxycholic Acid
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total Deoxycholic Acid | Month 6 | -0.59 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Deoxycholic Acid | Month 12 | -0.56 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Deoxycholic Acid | Month 18 | -0.51 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Deoxycholic Acid | Month 24/EOT | -0.59 umol/L |
Secondary
Median Change From Baseline In Total Endogenous Bile Acid
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total Endogenous Bile Acid | Month 6 | -0.83 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Endogenous Bile Acid | Month 12 | -0.77 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Endogenous Bile Acid | Month 18 | -2.19 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Endogenous Bile Acid | Month 24/EOT | -2.02 umol/L |
Secondary
Median Change From Baseline In Total LDL Particles
Results are reported in nanomoles per liter (nmol/L).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total LDL Particles | Week 4 | 108.0 nmol/L |
| Primary Treatment Phase | Median Change From Baseline In Total LDL Particles | Week 8/EOT | 128.0 nmol/L |
| Primary Treatment Phase | Median Change From Baseline In Total LDL Particles | Week 12 | 159.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 6 (Small) | 148.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 12 (Small) | 89.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 18 (Small) | 18.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 24/EOT (Small) | 34.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Last Dose (Small) | 22.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 6 (Large) | 9.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 12 (Large) | -53.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 18 (Large) | -18.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 24/EOT (Large) | -122.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Last Dose (Large) | -8.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 6 (Intermediate-density Lipoprotein [IDL]) | -12.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 12 (IDL) | -57.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 18 (IDL) | -43.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Month 24/EOT (IDL) | 78.0 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total LDL Particles | Last Dose (IDL) | 11.0 nmol/L |
Secondary
Median Change From Baseline In Total Lithocholic Acid
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total Lithocholic Acid | Month 6 | 0.00 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Lithocholic Acid | Month 12 | 0.00 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Lithocholic Acid | Month 18 | 0.00 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Lithocholic Acid | Month 24/EOT | 0.00 umol/L |
Secondary
Median Change From Baseline In Total Triglycerides
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total Triglycerides | Week 4 | -0.0226 mmol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Triglycerides | Week 8/EOT | 0.0565 mmol/L |
| Primary Treatment Phase | Median Change From Baseline In Total Triglycerides | Week 12 | 0.1130 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Triglycerides | Month 6 | -0.1469 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Triglycerides | Month 12 | -0.0113 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Triglycerides | Month 18 | -0.0565 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Triglycerides | Month 24/EOT | 0.000 mmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In Total Triglycerides | Last Dose | -0.068 mmol/L |
Secondary
Median Change From Baseline In Total UDCA
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Total UDCA | Month 6 | -0.34 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total UDCA | Month 12 | -0.47 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total UDCA | Month 18 | -2.89 umol/L |
| Primary Treatment Phase | Median Change From Baseline In Total UDCA | Month 24/EOT | -1.68 umol/L |
Secondary
Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol
Results are reported in milligrams per deciliter (mg/dL).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol | Week 12 | 5.0 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol | Month 6 | -21.0 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol | Month 12 | -7.0 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol | Month 18 | -14.0 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol | Month 24/EOT | -1.0 mg/dL |
| Long-term Safety Extension Phase | Median Change From Baseline In Very Low-density Lipoprotein (VLDL) Cholesterol | Last Dose | -11.5 mg/dL |
Secondary
Median Change From Baseline In VLDL Particles
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In VLDL Particles | Week 4 | -5.55 nmol/L |
| Primary Treatment Phase | Median Change From Baseline In VLDL Particles | Week 8/EOT | 2.70 nmol/L |
| Primary Treatment Phase | Median Change From Baseline In VLDL Particles | Week 12 | -0.90 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particles | Month 6 | -4.70 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particles | Month 12 | -6.20 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particles | Month 18 | -6.80 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particles | Month 24/EOT | -0.30 nmol/L |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particles | Last Dose | -6.80 nmol/L |
Secondary
Median Change From Baseline In VLDL Particle Size
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Median Change From Baseline In VLDL Particle Size | Week 4 | 42.55 nm |
| Primary Treatment Phase | Median Change From Baseline In VLDL Particle Size | Week 8/EOT | 43.40 nm |
| Primary Treatment Phase | Median Change From Baseline In VLDL Particle Size | Week 12 | 45.10 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particle Size | Month 6 | -4.80 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particle Size | Month 12 | -3.50 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particle Size | Month 18 | -4.90 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particle Size | Month 24/EOT | 0.50 nm |
| Long-term Safety Extension Phase | Median Change From Baseline In VLDL Particle Size | Last Dose | -4.10 nm |
Secondary
Median Change From Week 8 In HDL Cholesterol Concentration At Week 12
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Treatment Phase | Median Change From Week 8 In HDL Cholesterol Concentration At Week 12 | 0.3108 mmol/L |
Secondary
Median Change From Week 8 In HDL Particle Number At Week 12
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Treatment Phase | Median Change From Week 8 In HDL Particle Number At Week 12 | 1.40 umol/L |
Secondary
Median Change From Week 8 In HDL Particle Size At Week 12
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Primary Treatment Phase | Median Change From Week 8 In HDL Particle Size At Week 12 | 0.30 nm |
Secondary
Participants With Lipoprotein X
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Primary Treatment Phase | Participants With Lipoprotein X | Week 12 | 1 Participants |
| Primary Treatment Phase | Participants With Lipoprotein X | Last Dose | 0 Participants |
| Long-term Safety Extension Phase | Participants With Lipoprotein X | Week 12 | 0 Participants |
| Long-term Safety Extension Phase | Participants With Lipoprotein X | Last Dose | 0 Participants |
Secondary
Time To Reach Cmax (Tmax) For OCA And Conjugates
Results are reported in hours (h).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Primary Treatment Phase | Time To Reach Cmax (Tmax) For OCA And Conjugates | OCA | 1.00 h |
| Primary Treatment Phase | Time To Reach Cmax (Tmax) For OCA And Conjugates | Glyco-OCA | 5.00 h |
| Primary Treatment Phase | Time To Reach Cmax (Tmax) For OCA And Conjugates | Tauro-OCA | 5.98 h |
| Primary Treatment Phase | Time To Reach Cmax (Tmax) For OCA And Conjugates | Total-OCA | 5.00 h |