Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cholangitis
- Conditions
- Liver Cirrhosis, Biliary
- Interventions
- Drug: Obeticholic Acid (OCA)Drug: Placebo
- Registration Number
- NCT02308111
- Lead Sponsor
- Intercept Pharmaceuticals
- Brief Summary
Primary Biliary Cholangitis (PBC) is a serious, life-threatening, bile acid related liver disease of unknown cause. Without treatment, it frequently progresses to liver fibrosis and eventual cirrhosis requiring liver transplantation or resulting in death. The investigational drug, Obeticholic Acid (OCA) is a modified bile acid and FXR agonist that is derived from the primary human bile acid chenodeoxycholic acid. The key mechanisms of action of OCA, including its choleretic, anti-inflammatory, and anti-fibrotic properties, underlie its hepatoprotective effects and result in attenuation of injury and improved liver function in a cholestatic liver disease such as PBC. The study will assess the effect of OCA compared to placebo, combined with stable standard care, on clinical outcomes in PBC participants.
- Detailed Description
This Phase 4, double-blind, randomized, placebo-controlled, multicenter study is being undertaken at up to 170 sites internationally to evaluate the effect of OCA on clinical outcomes in 428 participants with PBC. The study will include a screening period of up to 8 weeks, requiring two clinic visits. Eligible participants will be randomly allocated (1:1) to treatment with either OCA 5 mg or matching placebo tablets, taken orally once daily for the majority of participants; dose and frequency will be modified for participants with cirrhosis and classified as Child-Pugh (CP) B or C. Randomization will be stratified by standard treatment with UDCA (yes/no) and baseline liver function. The treatment period involves clinic visits approximately every 3 months. At the 3 month visit or any study visit thereafter, if study treatment is tolerated, participants' dose should be titrated per protocol in a blinded manner eg for participants who are non-cirrhotic or classified as CP A and randomized to OCA, they should receive the maximum daily dose of 10 mg OCA, those on placebo continue to receive placebo. Subsequently, daily dosage may return to 5 mg if necessary for these participants who are non-cirrhotic or classified as CP A, but should be increased to 10 mg if possible, based on tolerability and clinical judgment. Safety and tolerability will be assessed by monitoring adverse events and vital signs, and blood and urine testing. The study is event driven and total duration will be determined by the time required to accrue approximately 127 primary endpoint events, estimated to be approximately 10 years. Participants are expected to have a minimum follow-up time of approximately 6 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 334
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Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Diseases [AASLD] and the European Association for the Study of the Liver [EASL] practice guidelines; Lindor 2009; EASL 2009), as demonstrated by the presence of ≥2 of the following 3 diagnostic factors:
- History of elevated Alkaline phosphatase levels for at least 6 months
- Positive antimitochondrial antibody (AMA) titer or if AMA negative or in low titer (<1:80) PBC-specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
- Liver biopsy consistent with PBC
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A mean total bilirubin >ULN and ≤5x ULN and/or a mean ALP >3x ULN
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Either is not taking UDCA (no UDCA dose in the past 3 months) or has been taking UDCA for at least 12 months with a stable dose for ≥3 months prior to Day 0
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History or presence of other concomitant liver diseases including:
- Hepatitis C virus infection
- Active Hepatitis B infection; however, subjects who have seroconverted (hepatitis B surface antigen and hepatitis B e antigen negative) may be included in this study after consultation with the medical monitor
- Primary sclerosing cholangitis (PSC)
- Alcoholic liver disease
- Definite autoimmune liver disease or overlap hepatitis
- Nonalcoholic steatohepatitis (NASH)
- Gilbert's Syndrome
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Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:
-
History of liver transplant, current placement on a liver transplant list, or current Model of End Stage Liver Disease (MELD) score >12. Subjects who are placed on a transplant list despite a relatively early disease stage (for example per regional guidelines) may be eligible as long as they do not meet any of the other exclusion criteria
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Cirrhosis with complications, including history (within the past 12 months) or presence of:
- Variceal bleed
- Uncontrolled ascites
- Encephalopathy
- Spontaneous bacterial peritonitis
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Known or suspected HCC
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Prior transjugular intrahepatic portosystemic shunt procedure
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Hepatorenal syndrome (type I or II) or screening (Visit 1 or 2) serum creatinine >2 mg/dL (178 μmol/L)
-
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Mean total bilirubin >5x ULN
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Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures
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Other medical conditions that may diminish life expectancy, including known cancers (except carcinomas in situ or other stable, relatively benign conditions)
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If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
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Known history of human immunodeficiency virus infection
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Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months)
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Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study
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History of alcohol abuse or other substance abuse within 1 year prior to Day 0
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Participation in another investigational product, biologic, or medical device study within 30 days prior to Screening. Participation in a previous study of OCA is allowed with 3 months washout prior to enrollment in this study
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Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain
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History of known or suspected clinically significant hypersensitivity to OCA or any of its components
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UDCA naïve (unless contraindicated)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Obeticholic Acid (OCA) 5 mg to 10 mg Obeticholic Acid (OCA) Obeticholic Acid (OCA) 5 mg for a minimum 3 months and then titrating up to a maximum 10 mg for the remainder of the trial (based on tolerability and CP Score). Placebo Placebo -
- Primary Outcome Measures
Name Time Method Time to the First Occurrence of Composite Endpoint Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years) To assess the effect of OCA, compared to placebo in conjunction with the established local standard of care, on clinical outcomes in participants with PBC as measured by time to the first occurrence of any of the following adjudicated events, derived as a composite event endpoint of death, liver transplant, model of end-stage liver disease (MELD) ≥15, uncontrolled ascites, or hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy (as defined by a West Haven score of \>=2), or spontaneous bacterial peritonitis. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% confidence intervals (CIs) for the clinical events distribution percentiles (25th and 50th) are provided.
Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint) Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years) Primary clinical outcome event is the first occurrence of the following events: death, liver transplant, MELD score \>=15 (MELD-Na score \>=12 baseline), MELD-Na score \>=15 (MELD-Na score \<12 baseline), hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis), or bacterial empyema, uncontrolled or refractory ascites (requiring large volume paracentesis), portal hypertension syndromes, progression to decompensated liver disease, and progression to clinical evidence of portal hypertension without decompensation (for participants without decompensation or clinical evidence of portal hypertension at baseline). 71 endpoint events were observed in the OCA arm, and 80 were observed in the Placebo arm. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided.
- Secondary Outcome Measures
Name Time Method Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint Time to first occurrence from date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to 7 years) The first occurrence of the key secondary clinical event refers to the first occurrence of the following events: death, liver transplant, MELD-Na score \>=15 if MELD-Na\< 12 at baseline, MELD score \>=15 if MELD-Na \>=12 at baseline, uncontrolled or refractory ascites, portal hypertension syndromes (hepatorenal syndrome, portopulmonary syndrome, hepatopulmonary syndrome) or hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis, or bacterial empyema. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided.
Time To Liver Transplant Or Death (All-cause) Time to first occurrence from date of randomization until the date of first documented liver transplant or date of death from any cause (up to 7 years) The effect of OCA compared to placebo on time to liver transplant or death (all-cause) was assessed. The events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided.
Time to First Occurrence of Fatal Event (All-Cause) Time to first occurrence from date of randomization until the date of death from any cause (up to 7 years) The results represent the ratio of OCA to placebo. The fatal events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the fatal events distribution percentiles (25th and 50th) are provided
Time to First Occurrence of Liver Transplant Time to first occurrence from date of randomization until the date of first documented liver transplant or date of death from any cause (up to 5 years) The effect of OCA compared to placebo on time to occurrence of a liver transplant was assessed. The results represented the ratio of OCA to placebo. A hazard ratio \<1 indicated an advantage for OCA. The event of interest was summarized through Cumulative Incidence Function (CIF) estimate at 5 years.
Time to First Occurrence of Hospitalization Due to Hepatic Events Time to first occurrence from date of randomization until the date of hospitalization, liver transplant or death from any cause, whichever came first (up to 5 years) Hospitalization events include new onset or recurrent variceal bleed, hepatic encephalopathy (as defined by a West Haven score of \>=2), spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis OR presence of \>250/mm\^3 polymorph leucocytes \[PMNs\] in the ascitic fluid), bacterial empyema is confirmed by diagnostic thoracentesis OR presence of \>250/mm\^3 PMNs in the pleural fluid. The event of interest was summarized through CIF estimate at 5 years.
Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18) Baseline up to Month 72 Markers of inflammation, which include CK-18, were assessed.
Time to First Occurrence of Uncontrolled or Refractory Ascites Time to first occurrence from date of randomization until the date of first documented uncontrolled or refractory ascites, liver transplant or date of death from any cause, whichever came first (up to 5 years) Uncontrolled or refractory ascites are defined as diuretic-resistant ascites requiring large-volume paracentesis. The effect of OCA compared to placebo on time to the first occurrence of uncontrolled or refractory ascites was assessed. The event of interest was summarized through CIF estimate at 5 years.
Time to First Occurrence of MELD Score ≥15 Time to first occurrence from date of randomization until the date of first documented MELD Score ≥15, liver transplant or date of death from any cause, whichever came first (up to 5 years) The MELD score is useful in assessing participants with significant decompensation. The MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and International Normalized Ratio (INR), as appropriate, to predict survival. The MELD score ranges from 6 to 40. The higher the score, the more likely a participant will receive a liver from a deceased donor when an organ becomes available. The event of interest was summarized through CIF estimate at 5 years.
Time To Development Of Varix/Varices Time to first occurrence from date of randomization until the date of first documented development of varix/varices, liver transplant or death from any cause, whichever came first (up to 5 years) The effect of OCA compared to placebo on time to development of varix/varices was assessed. The event of interest was summarized through CIF estimate at 5 years.
Time To Liver-Related Death Time to first occurrence from date of randomization until the date of first liver-related or non-liver- related death, whichever came first (up to 5 years) The effect of OCA compared to placebo on time to liver-related death was assessed. The event of interest was summarized through CIF estimate at 5 years.
Time To Liver-Related Death Or Liver Transplant Time to first occurrence from date of randomization until the date of liver transplant, liver-related death or non-liver-related death from any cause, whichever came first (up to 5 years) The effect of OCA compared to placebo on time to liver-related death or liver transplant was assessed. The event of interest was summarized through CIF estimate at 5 years.
Time To Liver-Related Death, Liver Transplant, Or MELD Score ≥15 Time to first occurrence from date of randomization until the date of liver transplant, liver-related death, non-liver-related death from any cause or MELD Score ≥15, whichever came first (up to 5 years) The effect of OCA compared to placebo on time to liver-related death, liver transplant, or MELD Score ≥15 was assessed. The MELD score is useful in assessing participants with significant decompensation. The MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and INR, as appropriate, to predict survival. The MELD score ranges from 6 to 40. The higher the score, the more likely a participant will receive a liver from a deceased donor when an organ becomes available. The event of interest was summarized through CIF estimate at 5 years.
Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline) Time to first occurrence from date of randomization until the date of cirrhosis, liver transplant or death from any cause, whichever came first (up to 5 years) When a participant is identified as noncirrhotic at the Baseline and exhibited any signs or symptoms associated with progression to cirrhosis, the participant was assessed by Fibroscan® TE where available. The event of interest was summarized through CIF estimate at 5 years.
Time To Occurrence Of Hepatocellular Carcinoma (HCC) Time to first occurrence from date of randomization until the date of HCC diagnosis, liver transplant or death from any cause, whichever came first (up to 5 years) The effect of OCA compared to placebo on time to occurrence of HCC was assessed. The event of interest was summarized through CIF estimate at 5 years.
Change From Baseline To Month 24 Of Total Bilirubin Baseline up to Month 24 Liver biochemistry, which includes total bilirubin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using mixed model repeated measures (MMRM), including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
Change From Baseline To Month 24 Of Direct Bilirubin Baseline up to Month 24 Liver biochemistry, which includes direct bilirubin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
Change From Baseline To Month 72 Of 7α-hydroxy-4-cholesten-3-one (C4) Baseline up to Month 72 Markers of hepatic fibrosis, which include C4, were assessed.
Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST) Baseline up to Month 24 Liver biochemistry, which includes AST, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT) Baseline up to Month 24 Liver biochemistry, which includes ALT, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP) Baseline up to Month 24 Liver biochemistry, which includes ALP, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT) Baseline up to Month 24 Liver biochemistry, which includes GGT, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
Change From Baseline To Month 24 Of Albumin Baseline up to Month 24 Liver biochemistry, which includes albumin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
Change From Baseline To Month 24 Of INR Baseline up to Month 24 The coagulation test, which includes INR, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. INR is the ratio of tested prothrombin time to normal prothrombin time, to a power designated the international sensitivity index (ISI). INR normal range is 0.8 to 1.2 (female and male). Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
Change From Baseline To Month 72 Of MELD Score Baseline up to Month 72 The MELD score is useful in assessing participants with significant decompensation. The MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and INR, as appropriate, to predict survival. The MELD score ranges from 6 to 40. The higher the score, the more likely a participant will receive a liver from a deceased donor when an organ becomes available.
Change From Baseline To Month 72 Of MELD-Na Score Baseline up to Month 72 The MELD-Na score is another useful predictor in assessing participants with significant decompensation. The MELD-Na took into account the effect of serum sodium as a reflection of renal function and hypothetically may improve the accuracy of the model score. The MELD-Na score is derived from the participant's serum total bilirubin, serum creatinine, INR, and serum sodium, as appropriate, to predict survival. The MELD-Na score ranges from 6 to 40. The higher the score, the more likely a participant will receive a liver from a deceased donor when an organ becomes available.
Change From Baseline To Month 72 Of CPS Baseline up to Month 72 Child-Pugh Score (Pugh 1973, Lucey 1997) was calculated and reported within the electronic data capture (EDC) system based on data entered into the CRF by adding the scores from the 5 factors and could have ranged from 5 to15. A total score of 5 to 6 was considered Grade A (mild, well-compensated disease); 7 to 9 was Grade B (moderate, significant functional compromise); and 10 and above was Grade C (severe, decompensated disease).
Change From Baseline To Month 72 Of Mayo Risk Score (MRS) Baseline up to Month 72 Mayo Risk Score (MRS) was calculated and reported within the EDC system. Calculation of MRS included Investigator assessment of peripheral edema and the use of diuretic therapy, which was assessed during the adverse event and concomitant medicine review at the scheduled visits and entered into the CRF, as well as total bilirubin, albumin, and prothrombin time results obtained from the central laboratory data. There is no maximum and minimum range of score but an increase in the MRS represents an increase in the risk of death.
Change From Baseline To Month 72 Of Immunoglobulin-M (IgM) Baseline up to Month 72 Markers of inflammation, which include IgM, were assessed.
Change From Baseline To Month 72 Of C-reactive Protein (CRP) Baseline up to Month 72 Markers of inflammation, which include CRP, were assessed.
Change From Baseline To Month 72 Of Tumor Necrosis Factor-α (TNF-α) Baseline up to Month 72 Markers of inflammation, which include TNF-α, were assessed.
Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19) Baseline up to Month 72 Markers of hepatic fibrosis, which include FGF-19, were assessed.
Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF) Baseline up to Month 72 Liver fibrosis was assessed using ELF test. The ELF test assessed: hyaluronic acid, procollagen3 N-terminal peptide, and a tissue inhibitor of metalloproteinase 1. The ELF test is a composite score: \< 7.7: no to mild fibrosis; ≥ 7.7 - \< 9.8: Moderate fibrosis; ≥ 9.8 - \< 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline suggests decreased fibrosis.
Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography Baseline up to Month 72 Hepatic stiffness was measured using non-invasive transient Elastography with Fibroscan® TE device.
PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Baseline up to the last IP dose plus 30 days and prior to commercial OCA initiation date (up to 7 years) An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as AEs that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Pharmacokinetic (PK) Population: Fasting Trough Concentrations Of OCA By Dose Regimen Months 3, 6, 9, 12, 24, 36, 48, and 60 The fasting trough PK concentrations of OCA of different dose regimens taken throughout the study are reported.
PK Population: Serial Concentration of OCA By Dose Regimen Month 9 In Month 9, blood samples were collected at predose, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h and PK serial concentrations at different dose regimen are reported.
PK Population: Area Under The Concentration-Time Curve (AUC) From 0 to 6 Hours Post-dose (AUC0-6h) Of Participants Who Received 5 mg QD OCA and With CP Score=Non-Cirrhotic (NC) Month 9 In Month 9, blood samples were collected at predose, 0.5h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
PK Population: AUC From 0 to 24 Hours Post-dose (AUC0-24h) Of Participants Who Received 5 mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose, 0.5h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
PK Population: Maximum Observed Concentration (Cmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
PK Population: Time to Cmax (Tmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
PK Population: Metabolite to Parent Ratio of AUC0-6h (MRAUC) Of Participants Who Received 5mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
PK Population: Metabolite to Parent Ratio of Cmax (MRCmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CPS Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
PK Population: Cmax Of Participants Who Received 5mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
PK Population: Tmax Of Participants Who Received 5mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
PK Population: Concentration at 24 Hours Post-dose (Ctrough) Of Participants Who Received 5mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
PK Population: MRAUC Of Participants Who Received 5mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
PK Population: MRCmax Of Participants Who Received 5mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
PK Population: Ctrough Of Participants Who Received 5mg QD OCA and With CP Score=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=B.
PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC
PK Population: Cmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
PK Population: Tmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
PK Population: Ctrough Of Participants Who Received 5mg QOD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
PK Population: MRAUC Of Participants Who Received 5mg QOD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
PK Population: MRCmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CP Score=NC Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CPS Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With CP Score=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With CP Score=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B
PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
PK Population: Cmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
PK Population: Tmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
PK Population: Ctrough Of Participants Who Received 5 mg QOD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
PK Population: MRAUC Of Participants Who Received 5 mg QOD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QD OCA Months 6, 9, 12, 24, 36, and 60 The trough concentration of OCA in the cirrhotic participants who received 10 mg QD OCA was reported.
PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
PK Population: MRCmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A
PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B Month 9 In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QD OCA Months 3, 6, 12, 24, and 48 The trough concentration of OCA in the cirrhotic participants who received 5 mg QD OCA was reported.
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QD OCA Months 3, 6, 9, 12, and 24 The trough concentration of OCA in the non-cirrhotic participants who received 5 mg QD OCA was reported.
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QOD OCA Months 6, 12, and 24 The trough concentration of OCA in the cirrhotic participants who received 5 mg QOD OCA was reported.
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QOD OCA Months 3, 6, and 12 The trough concentration of OCA in the non-cirrhotic participants who received 5 mg QOD OCA was reported.
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QW OCA Months 6 and 12 The trough concentration of OCA in the cirrhotic participants who received 5 mg QW OCA was reported.
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QW OCA Month 12 In Month 12, the trough concentration of OCA in the non-cirrhotic participants who received 5 QW QOD OCA was reported.
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg Q2W OCA Months 6, 24, 36 and 48 The trough concentration of OCA in the cirrhotic participants who received 5 mg Q2W OCA was reported.
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg Q2W OCA Months 3, 6, 12, 24, 36, and 48 The trough concentration of OCA in the non-cirrhotic participants who received 5 Q2W QOD OCA was reported.
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QD OCA Months 6, 9, 12, 24, and 36 The trough concentration of OCA in the non-cirrhotic participants who received 10 QD QOD OCA was reported.
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QOD OCA Months 3, 6, 9, 12, 24, 36, 48, and 60 PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QOD OCA Month 12 In Month 12, the trough concentration of OCA in the non-cirrhotic participants who received 10 mg QOD OCA was reported.
PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg Q2W OCA Month 6 In Month 6, the trough concentration of OCA in the cirrhotic participants who received 10 mg Q2W OCA was reported.
PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg Q2W OCA Month 6 In Month 6, the trough concentration of OCA in the non-cirrhotic participants who received 10 mg Q2W OCA was reported.
Trial Locations
- Locations (180)
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Gastrointestinal Specialists of Georgia
🇺🇸Marietta, Georgia, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Flinders Medical Centre
🇦🇺Adelaide, South Australia, Australia
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
St. Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Hospital das Clinicas da Universidade Federal de Minas Gerais (UFMG)
🇧🇷Belo Horizonte,, Minas Gerais, Brazil
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Schiff Center for Liver Diseases/University of Miami
🇺🇸Miami, Florida, United States
Indianapolis Gastroenterology Research Foundation
🇺🇸Indianapolis, Indiana, United States
Quality Medical Research, PLLC
🇺🇸Nashville, Tennessee, United States
UT Health The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Baylor College of Medicine - Advanced Liver Therapies
🇺🇸Houston, Texas, United States
American Research Corporation at Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Azienda Socio-Sanitarla Territoriale (ASST) Santi Paolo e Carlo
🇮🇹Milano, Italy
Azienda Socio Sanitaria Territoriale (ASST) di Monza
🇮🇹Monza, Italy
Università Politecnica delle Marche - Azienda Ospedaliero
🇮🇹Ancona, Italy
Policlinico Universitario Agostino Gemelli - Universita Cattolica del Sacro Cuore
🇮🇹Rome, Italy
Nzoz Vitamed
🇵🇱Bydgoszcz, Kujawsko-Pomorskie, Poland
Medical University of Warsaw Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie (SPCSK in Warsaw
🇵🇱Warsaw, Masovia, Poland
Amsterdam University Medical Centre (AMC)
🇳🇱Amsterdam, Netherlands
NZ Liver Transplant Unit, Auckland Hospital
🇳🇿Grafton, Auckland, New Zealand
Wojewodzki Szpital Specjalistyczny im. J. Gromkowskiego, Pierwszy Oddzial Chorob Zakaznych
🇵🇱Wroclaw, Lover Silesia, Poland
Dep. Of Gastroenterology UM Lublin
🇵🇱Lublin, Poland
Centro Hospitalar Lisboa Norte, EPE - Hospital de Santa Maria
🇵🇹Lisbon, Portugal
Hospital Universitario Marqués De Valdecilla
🇪🇸Santander, Cantabria, Spain
Inselspital, University Of Bern, UVCM, DMLL
🇨🇭Bern, Switzerland
University Hospitals Bristol NHS Foundation Trust
🇬🇧Bristol, Avon, United Kingdom
Ege University School of Medicine Gastroenterology Dept.
🇹🇷Izmir, Turkey
Plymouth Hospitals NHS Trust, Derriford Hospital
🇬🇧Plymouth, Devon, United Kingdom
Forth Valley Royal Hospital
🇬🇧Larbert, Scotland, United Kingdom
Cambrigde University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, West Midlands, United Kingdom
The Royal Free Hospital
🇬🇧London, United Kingdom
London Health Sciences Centre-University Hospital
🇨🇦London, Ontario, Canada
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
University of California Davis, Davis Medical Center
🇺🇸Sacramento, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Piedmont Atlanta Hospital
🇺🇸Atlanta, Georgia, United States
Henry Ford Health System
🇺🇸Novi, Michigan, United States
Hospital De Clinicas University Of Buenos Aires
🇦🇷Buenos Aires, Argentina
Stanford University
🇺🇸Stanford, California, United States
Clinical Research Centers of America
🇺🇸Murray, Utah, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Southern Therapy and Advanced Research (STAR)
🇺🇸Jackson, Mississippi, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Centro De Hepatología
🇦🇷La Plata, Buenos Aires, Argentina
Swedish Organ Transplant & Liver Center
🇺🇸Seattle, Washington, United States
Baylor Scott and White Research Institute
🇺🇸Fort Worth, Texas, United States
Hospital Privado Universitario de Cordoba S.A.
🇦🇷Córdoba, Cordoba, Argentina
Department of Gastroenterology & Hepatology, Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
University Hospital Antwerp
🇧🇪Edegem, Antwerp, Belgium
Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
Cepec Huufma
🇧🇷Sao Luis, Maranhao, Brazil
Instituto Goiano de Gastroenterologia
🇧🇷Goiânia, Goias, Brazil
Hospital Universitario Professor Edgard Santos
🇧🇷Bahia, Salvador, Brazil
Instituto Hospital de Base do Distrito Federal-IHBDF
🇧🇷Brasilia, Distrito Federal Brazil, Brazil
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Cub Hôpital Erasme
🇧🇪Bruxelles, Belgium
University Hospital Ghent
🇧🇪Ghent, Belgium
Hospital Sao Rafael
🇧🇷São Salvador, Bahia, Brazil
University of Calgary Liver Unit (Heritage Medical Research Clinic)
🇨🇦Calgary, Alberta, Canada
Medicinsk klinik for mave, tarm-og leversygdomme
🇩🇰København Ø, Denmark
Odense University Hospital Afdeling for medicinske mave-tarmsygdomme S
🇩🇰Odense, Denmark
University Of Manitoba, Health Sciences Centre
🇨🇦Winnipeg, Manitoba, Canada
St. Ivan Rilsky University Hospital
🇧🇬Sofia, Bulgaria
East Tallinn Central Hospital Gastroenterology Center
🇪🇪Tallinn, Harju, Estonia
Tartu University Hospital
🇪🇪Tartu, Estonia
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
CHRU Hôpital HURIEZ
🇫🇷Lille, France
Chu De Bordeaux - Hôpital Haut Lévêque
🇫🇷Pessac Cedex, France
AOU Policlinico Sant' Orsola Malpighi
🇮🇹Bologna, Italy
Hadassah Hebrew University Medical Center
🇮🇱Jerusalem, Nazareth Elit, Israel
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
La Fe, Hospital ( Valence )
🇪🇸Valence, Spain
Klinikum der Johann-Wolfgang Goethe, Universitaet Frankfurt am Main
🇩🇪Frankfurt am Main, Hessen, Germany
Universität Leipzig KöR, Medizinische Fakultät
🇩🇪Leipzig, Germany
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Sourasky Tel-Aviv Medical Center
🇮🇱Tel-Aviv, Israel
Gastroenterology, Christchurch Hospital
🇳🇿Christchurch, Canterbury, New Zealand
Hospital Universitario Austral
🇦🇷Presidente Derqui, Buenos Aires, Argentina
Dim Clínica Privada
🇦🇷Ramos Mejía, Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
Univeritatsklinikum Hamburg Eppendorf, Medizinische Klinik und Poliklinik
🇩🇪Hamburg, Germany
University of Munich, LMU Klinikum Grosshadern
🇩🇪Munich, Germany
University of Colorado Denver and Hospital
🇺🇸Aurora, Colorado, United States
UF Hepatology Research at CTRB
🇺🇸Gainesville, Florida, United States
UMass Medical School
🇺🇸Worcester, Massachusetts, United States
Tulane University Medical Center
🇺🇸New Orleans, Louisiana, United States
University of Louisville, Medical Dental Complex
🇺🇸Louisville, Kentucky, United States
Minnesota Gastroenterology, P.A.
🇺🇸Saint Paul, Minnesota, United States
Saint Louis University Gastroenterology & Hepatology
🇺🇸Saint Louis, Missouri, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Mount Sinai Beth Israel
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
The Liver Institute at Methodist Dallas Medical Center
🇺🇸Dallas, Texas, United States
Texas Digestive Disease Consultants
🇺🇸Southlake, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
McGuire DVAMC
🇺🇸Richmond, Virginia, United States
CIPREC - Centro de Investigacion y Prevencion Cardiovascular S.A.
🇦🇷Buenos Aires, Argentina
Centrol Integral de Gastroenterologia
🇦🇷Buenos Aires, Argentina
Hospital Aleman
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
Hospital Britanico De Buenos Aires
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Fiona Stanley Hospital, Gastroenterology Department
🇦🇺Murdoch, Western Australia, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Gallipoli Medical Research Foundation
🇦🇺Brisbane, Queensland, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
AKH, Medical University of Vienna
🇦🇹Vienna, Austria
Uz Leuven
🇧🇪Leuven, Vlaams-Brabant, Belgium
Gastrocentro/ Universidade Estadual de Campinas (UNICAMP)
🇧🇷Sao Paulo, Campinas, Brazil
Gastrocentro. Unidad Estadual de CAmpinas UNICAMP
🇧🇷Campinas, Sao Paulo, Brazil
Universidade Federal do Estado do Rio de Janeiro - Hospital Universitario Gaffree e Guinle/HUGG/UNIRIO
🇧🇷Rio de Janeiro, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP
🇧🇷Sao Paulo, Brazil
University Health Network, Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Chum
🇨🇦Montreal, Quebec, Canada
Aarhus University Hospital Department of Hepatology and Gastroenterology
🇩🇰Aarhus, Aarhus C, Denmark
Hospital Saint-Antoine, A.P.-H.P.
🇫🇷Paris Cedex 12, Paris, France
Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
🇩🇪Hannover, Lower Saxony, Germany
CHARITÉ, Campus Virchow Klinikum
🇩🇪Berlin, Germany
Friedrich-Alexander-Uniersitat Erlangen
🇩🇪Erlangen, QLD, Germany
Universitaetsklinikum Heidelberg Medizinische Universitaetsklinik
🇩🇪Heidelberg, Germany
Queen Mary Hospital
🇭🇰Hong Kong, Pokfulam, Hong Kong
Humanity & Health Research Centre
🇭🇰Hong Kong, Hong Kong
Szent János Hospital
🇭🇺Budapest, Hungary
Békés Megyei Kozponti Korhaz - Dr. Rethy Pal Tagkorhaz
🇭🇺Bekescsaba, Hungary
University Of Debrecen, Department Of Medicine, Division Of Gastroenterology
🇭🇺Debrecen, Hungary
Rambam Health Care Campus
🇮🇱Haifa, Israel
Soroka Medical Center
🇮🇱Beer Sheva, Israel
Azienda Ospedaliero - Universitaria di Cagliari - Centro per lo Studio delle Malattie del Fegato
🇮🇹Monserrato, Cagliari, Italy
Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Azienda Ospedaliero Universitaria Careggi Universita di Firenze
🇮🇹Florence, Italy
Azienda Ospedaliero Universitaria Sant´ Orsola Malpighi
🇮🇹Bologna, Italy
AOU Ospedale Civile S. Agostino Estense - UO Medicina Metabolica
🇮🇹Modena, Italy
AOU Policlinico Paolo Giaccone - Di.Bi.M.I.S
🇮🇹Palermo, Italy
Azienda Ospedaliero - Universita di Padova
🇮🇹Padova, Italy
Inje University Busan Paik Hospital
🇰🇷Busan, Busanjin-gu, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Gangnam-gu, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Jongno-Gu, Korea, Republic of
Vilnius University Hospital Santaros klinikos
🇱🇹Vilnius, Lithuania
Pusan National University Hospital
🇰🇷Busan, Seo-gu, Korea, Republic of
Radboud UMC
🇳🇱Nijmegen, Gelderland, Netherlands
Vrije Universiteit Medisch Centrum (VUMC)
🇳🇱Amsterdam, Noord-Holland, Netherlands
Departamento De Gastroenterologia. Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran
🇲🇽Mexico City, DF, Mexico
Erasmus Mc
🇳🇱Rotterdam, Zuid Holland, Netherlands
Clinic For Gastroenterology And Hepatology Clinical Center Of Serbia
🇷🇸Belgrade, Serbia
Clinical Hospital Centre Zvezdara
🇷🇸Belgrade, Serbia
Oddział Gastr. I Hepat. Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibińskiego Sum
🇵🇱Katowice, Silesia, Poland
Hospital Universitario Puerta De Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Virgen De La Victoria University Hospital
🇪🇸Málaga, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Gothenburg, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Huddinge, Sweden
Ankara University School of Medicine Gastroenterology Dept.
🇹🇷Ankara, Turkey
Kantonsspital St. Gallen, Clinic for Gastroeterologie and Hepatologie
🇨🇭St. Gallen, Switzerland
Gartnavel General Hospital
🇬🇧Glasgow, Lanarkshire, United Kingdom
Institute of Cellular Medicine
🇬🇧Newcastle Upon Tyne, Tyne And Wear, United Kingdom
Nottingham University Hospital Nhs Trust
🇬🇧Nottingham, United Kingdom
Hospital of Lithuanian University of Health Sciences, Kauno klinikos
🇱🇹Kaunas, Lithuania
Consultorio Médico de la Dra Alma Laura Ladrón de Guevara Cetina
🇲🇽Mexico City, DF, Mexico
Turku University Central Hospital, Gastroenterology Outpatient Clinic
🇫🇮Turku,, Finland
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Centro De Investigaciones Clínicas Viña Del Mar
🇨🇱Viña Del Mar, V Región, Chile
Medica Sur, S.A.B. de C.V.
🇲🇽Ciudad de mexico, Ciudad De Mexico,, Mexico
Centrum Onkologii - Instytut im. Marii Skłodowskiej - Curie, Klinika Gastroenterologii Onkologicznej
🇵🇱Warsaw, Mazovia, Poland
USZ, Klinik für Gastroenterologie und Hepatologie
🇨🇭Zurich, Switzerland
Hospital Provincial del Centenario
🇦🇷Rosario, Santa Fe, Argentina
University of Alberta, Walter C. Mackenzie Health Sciences Centre (WMC)
🇨🇦Edmonton, Alberta, Canada
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands
Prince Of Wales Hospital
🇭🇰Hong Kong, Shatin, Hong Kong
Tuen Mun Hospital
🇭🇰Hong Kong, Tuen Mun, New Territories, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
🇭🇰Hong Kong, Hong Kong