Clinical trial NCT02308111: Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cholangitis
Official title: A Phase 4, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Effect of Obeticholic Acid on Clinical Outcomes in Patients With Primary Biliary Cholangitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Liver Cirrhosis, Biliary
Keywords: Primary Biliary Cirrhosis
PBC
Cirrhosis
Liver
Lead sponsor: Intercept Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-12-04
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria:

1. 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
2. A mean total bilirubin \>ULN and ≤5x ULN and/or a mean ALP \>3x ULN
3. 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

Exclusion Criteria:

1. 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
2. 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
   * Cirrhosis with complications, including history (within the past 12 months) or presence of:

     * Variceal bleed
     * Uncontrolled ascites
     * Encephalopathy
     * Spontaneous bacterial peritonitis
   * Known or suspected HCC
   * Prior transjugular intrahepatic portosystemic shunt procedure
   * Hepatorenal syndrome (type I or II) or screening (Visit 1 or 2) serum creatinine \>2 mg/dL (178 μmol/L)
3. Mean total bilirubin \>5x ULN
4. Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures
5. Other medical conditions that may diminish life expectancy, including known cancers (except carcinomas in situ or other stable, relatively benign conditions)
6. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
7. Known history of human immunodeficiency virus infection
8. Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months)
9. Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study
10. History of alcohol abuse or other substance abuse within 1 year prior to Day 0
11. 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
12. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain
13. History of known or suspected clinically significant hypersensitivity to OCA or any of its components
14. UDCA naïve (unless contraindicated)

Primary outcomes:
measure: Time to the First Occurrence of Composite Endpoint
timeFrame: Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years)
measure: Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint)
timeFrame: Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years)
Secondary outcomes:
measure: Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint
timeFrame: 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)
measure: Time To Liver Transplant Or Death (All-cause)
timeFrame: 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)
measure: Time to First Occurrence of Fatal Event (All-Cause)
timeFrame: Time to first occurrence from date of randomization until the date of death from any cause (up to 7 years)
measure: Time to First Occurrence of Liver Transplant
timeFrame: 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)
measure: Time to First Occurrence of Hospitalization Due to Hepatic Events
timeFrame: 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)
measure: Time to First Occurrence of Uncontrolled or Refractory Ascites
timeFrame: 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)
measure: Time to First Occurrence of MELD Score ≥15
timeFrame: 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)
measure: Time To Development Of Varix/Varices
timeFrame: 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)
measure: Time To Liver-Related Death
timeFrame: 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)
measure: Time To Liver-Related Death Or Liver Transplant
timeFrame: 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)
measure: Time To Liver-Related Death, Liver Transplant, Or MELD Score ≥15
timeFrame: 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)
measure: Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline)
timeFrame: 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)
measure: Time To Occurrence Of Hepatocellular Carcinoma (HCC)
timeFrame: 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)
measure: Change From Baseline To Month 24 Of Total Bilirubin
timeFrame: Baseline up to Month 24
measure: Change From Baseline To Month 24 Of Direct Bilirubin
timeFrame: Baseline up to Month 24
measure: Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST)
timeFrame: Baseline up to Month 24
measure: Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT)
timeFrame: Baseline up to Month 24
measure: Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP)
timeFrame: Baseline up to Month 24
measure: Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT)
timeFrame: Baseline up to Month 24
measure: Change From Baseline To Month 24 Of Albumin
timeFrame: Baseline up to Month 24
measure: Change From Baseline To Month 24 Of INR
timeFrame: Baseline up to Month 24
measure: Change From Baseline To Month 72 Of MELD Score
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of MELD-Na Score
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of CPS
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of Mayo Risk Score (MRS)
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of Immunoglobulin-M (IgM)
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of C-reactive Protein (CRP)
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of Tumor Necrosis Factor-α (TNF-α)
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19)
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18)
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of 7α-hydroxy-4-cholesten-3-one (C4)
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF)
timeFrame: Baseline up to Month 72
measure: Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography
timeFrame: Baseline up to Month 72
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to the last IP dose plus 30 days and prior to commercial OCA initiation date (up to 7 years)
measure: Pharmacokinetic (PK) Population: Fasting Trough Concentrations Of OCA By Dose Regimen
timeFrame: Months 3, 6, 9, 12, 24, 36, 48, and 60
measure: PK Population: Serial Concentration of OCA By Dose Regimen
timeFrame: Month 9
measure: 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)
timeFrame: Month 9
measure: 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
timeFrame: Month 9
measure: PK Population: Maximum Observed Concentration (Cmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Time to Cmax (Tmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Metabolite to Parent Ratio of AUC0-6h (MRAUC) Of Participants Who Received 5mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Metabolite to Parent Ratio of Cmax (MRCmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 5mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 5mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: Concentration at 24 Hours Post-dose (Ctrough) Of Participants Who Received 5mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 5mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 5mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 5mg QD OCA and With CP Score=B
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 5mg QOD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 5mg QOD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CPS Score=A
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CPS Score=A
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=A
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B
timeFrame: Month 9
measure: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QD OCA
timeFrame: Months 3, 6, 12, 24, and 48
measure: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QD OCA
timeFrame: Months 3, 6, 9, 12, and 24
measure: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QOD OCA
timeFrame: Months 6, 12, and 24
measure: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QOD OCA
timeFrame: Months 3, 6, and 12
measure: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QW OCA
timeFrame: Months 6 and 12
measure: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QW OCA
timeFrame: Month 12
measure: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg Q2W OCA
timeFrame: Months 6, 24, 36 and 48
measure: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg Q2W OCA
timeFrame: Months 3, 6, 12, 24, 36, and 48
measure: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QD OCA
timeFrame: Months 6, 9, 12, 24, 36, and 60
measure: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QD OCA
timeFrame: Months 6, 9, 12, 24, and 36
measure: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QOD OCA
timeFrame: Months 3, 6, 9, 12, 24, 36, 48, and 60
measure: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QOD OCA
timeFrame: Month 12
measure: PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg Q2W OCA
timeFrame: Month 6
measure: PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg Q2W OCA
timeFrame: Month 6
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Sacramento
country: United States
facility: University of California Davis, Davis Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Denver and Hospital
state: Colorado
city: Gainesville
country: United States
facility: UF Hepatology Research at CTRB
state: Florida
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Indianapolis Gastroenterology Research Foundation
state: Indiana
city: Louisville
country: United States
facility: University of Louisville, Medical Dental Complex
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Worcester
country: United States
facility: UMass Medical School
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Paul
country: United States
facility: Minnesota Gastroenterology, P.A.
state: Minnesota
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research (STAR)
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University Gastroenterology & Hepatology
state: Missouri
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Quality Medical Research, PLLC
state: Tennessee
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Advanced Liver Therapies
state: Texas
city: Houston
country: United States
facility: UT Health The University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at Texas Liver Institute
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Murray
country: United States
facility: Clinical Research Centers of America
state: Utah
city: Richmond
country: United States
facility: McGuire DVAMC
state: Virginia
city: Seattle
country: United States
facility: Swedish Organ Transplant & Liver Center
state: Washington
city: La Plata
country: Argentina
facility: Centro De Hepatología
state: Buenos Aires
city: Presidente Derqui
country: Argentina
facility: Hospital Universitario Austral
state: Buenos Aires
city: Ramos Mejía
country: Argentina
facility: Dim Clínica Privada
state: Buenos Aires
city: Córdoba
country: Argentina
facility: Hospital Privado Universitario de Cordoba S.A.
state: Cordoba
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: CIPREC - Centro de Investigacion y Prevencion Cardiovascular S.A.
city: Buenos Aires
country: Argentina
facility: Hospital De Clinicas University Of Buenos Aires
city: Buenos Aires
country: Argentina
facility: Centrol Integral de Gastroenterologia
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Hospital Aleman
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Hospital Britanico De Buenos Aires
city: Camperdown
country: Australia
facility: AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Department of Gastroenterology & Hepatology, Nepean Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Gallipoli Medical Research Foundation
state: Queensland
city: Adelaide
country: Australia
facility: Department of Gastroenterology and Hepatology, Royal Adelaide Hospital
state: South Australia
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital, Gastroenterology Department
state: Western Australia
city: Vienna
country: Austria
facility: AKH, Medical University of Vienna
city: Edegem
country: Belgium
facility: University Hospital Antwerp
state: Antwerp
city: Leuven
country: Belgium
facility: Uz Leuven
state: Vlaams-Brabant
city: Bruxelles
country: Belgium
facility: Cub Hôpital Erasme
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: São Salvador
country: Brazil
facility: Hospital Sao Rafael
state: Bahia
city: Sao Paulo
country: Brazil
facility: Gastrocentro/ Universidade Estadual de Campinas (UNICAMP)
state: Campinas
city: Brasilia
country: Brazil
facility: Instituto Hospital de Base do Distrito Federal-IHBDF
state: Distrito Federal Brazil
city: Goiânia
country: Brazil
facility: Instituto Goiano de Gastroenterologia
state: Goias
city: Sao Luis
country: Brazil
facility: Cepec Huufma
state: Maranhao
city: Belo Horizonte,
country: Brazil
facility: Hospital das Clinicas da Universidade Federal de Minas Gerais (UFMG)
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Bahia
country: Brazil
facility: Hospital Universitario Professor Edgard Santos
state: Salvador
city: Campinas
country: Brazil
facility: Gastrocentro. Unidad Estadual de CAmpinas UNICAMP
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: Universidade Federal do Estado do Rio de Janeiro - Hospital Universitario Gaffree e Guinle/HUGG/UNIRIO
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP
city: Sofia
country: Bulgaria
facility: St. Ivan Rilsky University Hospital
city: Calgary
country: Canada
facility: University of Calgary Liver Unit (Heritage Medical Research Clinic)
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta, Walter C. Mackenzie Health Sciences Centre (WMC)
state: Alberta
city: Winnipeg
country: Canada
facility: University Of Manitoba, Health Sciences Centre
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre-University Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Chum
state: Quebec
city: Viña Del Mar
country: Chile
facility: Centro De Investigaciones Clínicas Viña Del Mar
state: V Región
city: Aarhus
country: Denmark
facility: Aarhus University Hospital Department of Hepatology and Gastroenterology
state: Aarhus C
city: København Ø
country: Denmark
facility: Medicinsk klinik for mave, tarm-og leversygdomme
city: Odense
country: Denmark
facility: Odense University Hospital Afdeling for medicinske mave-tarmsygdomme S
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital Gastroenterology Center
state: Harju
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Turku,
country: Finland
facility: Turku University Central Hospital, Gastroenterology Outpatient Clinic
city: Paris Cedex 12
country: France
facility: Hospital Saint-Antoine, A.P.-H.P.
state: Paris
city: Lille
country: France
facility: CHRU Hôpital HURIEZ
city: Pessac Cedex
country: France
facility: Chu De Bordeaux - Hôpital Haut Lévêque
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann-Wolfgang Goethe, Universitaet Frankfurt am Main
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
state: Lower Saxony
city: Erlangen
country: Germany
facility: Friedrich-Alexander-Uniersitat Erlangen
state: QLD
city: Berlin
country: Germany
facility: CHARITÉ, Campus Virchow Klinikum
city: Hamburg
country: Germany
facility: Univeritatsklinikum Hamburg Eppendorf, Medizinische Klinik und Poliklinik
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg Medizinische Universitaetsklinik
city: Leipzig
country: Germany
facility: Universität Leipzig KöR, Medizinische Fakultät
city: Munich
country: Germany
facility: University of Munich, LMU Klinikum Grosshadern
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
state: Pokfulam
city: Hong Kong
country: Hong Kong
facility: Prince Of Wales Hospital
state: Shatin
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
state: Tuen Mun, New Territories
city: Hong Kong
country: Hong Kong
facility: Alice Ho Miu Ling Nethersole Hospital
city: Hong Kong
country: Hong Kong
facility: Humanity & Health Research Centre
city: Bekescsaba
country: Hungary
facility: Békés Megyei Kozponti Korhaz - Dr. Rethy Pal Tagkorhaz
city: Budapest
country: Hungary
facility: Szent János Hospital
city: Debrecen
country: Hungary
facility: University Of Debrecen, Department Of Medicine, Division Of Gastroenterology
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Medical Center
state: Nazareth Elit
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Sourasky Tel-Aviv Medical Center
city: Monserrato
country: Italy
facility: Azienda Ospedaliero - Universitaria di Cagliari - Centro per lo Studio delle Malattie del Fegato
state: Cagliari
city: Ancona
country: Italy
facility: Università Politecnica delle Marche - Azienda Ospedaliero
city: Bologna
country: Italy
facility: AOU Policlinico Sant' Orsola Malpighi
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Sant´ Orsola Malpighi
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi Universita di Firenze
city: Milano
country: Italy
facility: Azienda Socio-Sanitarla Territoriale (ASST) Santi Paolo e Carlo
city: Modena
country: Italy
facility: AOU Ospedale Civile S. Agostino Estense - UO Medicina Metabolica
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale (ASST) di Monza
city: Padova
country: Italy
facility: Azienda Ospedaliero - Universita di Padova
city: Palermo
country: Italy
facility: AOU Policlinico Paolo Giaccone - Di.Bi.M.I.S
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli - Universita Cattolica del Sacro Cuore
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
state: Busanjin-gu
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
state: Gangnam-gu
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-Gu
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
state: Seo-gu
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences, Kauno klinikos
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros klinikos
city: Ciudad de mexico
country: Mexico
facility: Medica Sur, S.A.B. de C.V.
state: Ciudad De Mexico,
city: Mexico City
country: Mexico
facility: Departamento De Gastroenterologia. Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran
state: DF
city: Mexico City
country: Mexico
facility: Consultorio Médico de la Dra Alma Laura Ladrón de Guevara Cetina
state: DF
city: Nijmegen
country: Netherlands
facility: Radboud UMC
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum (VUMC)
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Mc
state: Zuid Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centre (AMC)
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Grafton
country: New Zealand
facility: NZ Liver Transplant Unit, Auckland Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: Gastroenterology, Christchurch Hospital
state: Canterbury
city: Bydgoszcz
country: Poland
facility: Nzoz Vitamed
state: Kujawsko-Pomorskie
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. J. Gromkowskiego, Pierwszy Oddzial Chorob Zakaznych
state: Lover Silesia
city: Warsaw
country: Poland
facility: Medical University of Warsaw Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie (SPCSK in Warsaw
state: Masovia
city: Warsaw
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Skłodowskiej - Curie, Klinika Gastroenterologii Onkologicznej
state: Mazovia
city: Katowice
country: Poland
facility: Oddział Gastr. I Hepat. Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibińskiego Sum
state: Silesia
city: Lublin
country: Poland
facility: Dep. Of Gastroenterology UM Lublin
city: Lisbon
country: Portugal
facility: Centro Hospitalar Lisboa Norte, EPE - Hospital de Santa Maria
city: Belgrade
country: Serbia
facility: Clinic For Gastroenterology And Hepatology Clinical Center Of Serbia
city: Belgrade
country: Serbia
facility: Clinical Hospital Centre Zvezdara
city: Santander
country: Spain
facility: Hospital Universitario Marqués De Valdecilla
state: Cantabria
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta De Hierro Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Málaga
country: Spain
facility: Virgen De La Victoria University Hospital
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valence
country: Spain
facility: La Fe, Hospital ( Valence )
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
state: Huddinge
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Bern
country: Switzerland
facility: Inselspital, University Of Bern, UVCM, DMLL
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen, Clinic for Gastroeterologie and Hepatologie
city: Zurich
country: Switzerland
facility: USZ, Klinik für Gastroenterologie und Hepatologie
city: Ankara
country: Turkey
facility: Ankara University School of Medicine Gastroenterology Dept.
city: Izmir
country: Turkey
facility: Ege University School of Medicine Gastroenterology Dept.
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
state: Avon
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust, Derriford Hospital
state: Devon
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
state: Lanarkshire
city: Larbert
country: United Kingdom
facility: Forth Valley Royal Hospital
state: Scotland
city: Newcastle Upon Tyne
country: United Kingdom
facility: Institute of Cellular Medicine
state: Tyne And Wear
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: West Midlands
city: Cambridge
country: United Kingdom
facility: Cambrigde University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Free Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital Nhs Trust
Study officials:
affiliation: Intercept Pharmaceuticals
name: Erik Ness, MD
role: STUDY_DIRECTOR
References:
citation: Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.
citation: European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. No abstract available.