Clinical trial NCT03633227: Study of Obeticholic Acid (OCA) Evaluating Pharmacokinetics and Safety in Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment
Official title: A Phase 4, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Pharmacokinetics and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Liver Cirrhosis, Biliary
Keywords: Primary Biliary Cholangitis
Primary Biliary Cirrhosis
PBC
Hepatic Impairment
Cirrhosis
Liver
Lead sponsor: Intercept Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-08-16
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase 4, randomized, double-blind, placebo-controlled study will evaluate the pharmacokinetics (PK) and safety of OCA treatment in participants with PBC and moderate to severe hepatic impairment over a 48-week treatment period. Participants who have completed their 48-week double blind treatment period will continue double-blind treatment until all randomized participants have completed their 48-week treatment period and the database for that period is locked. An open-label extension study in which all participants receive OCA will be considered following review of blinded safety and PK data.


Eligibility criteria: Inclusion Criteria:

1. A definite or probable diagnosis of PBC (consistent with American Association for the Study of Liver Diseases \[AASLD\] and European Association for the Study of the Liver \[EASL\] Practice Guidelines, defined as having ≥2 of the following 3 diagnostic factors:

   * History of elevated alkaline phosphatase (ALP) levels for at least 6 months
   * Positive antimitochondrial antibody (AMA) titer or if AMA negative or low titer (≤1:80), PBC specific antibodies (anti-glycoprotein 210 \[GP210\] and/or anti-SP100) and/or antibodies against the major M2 components (E2 component of mitochondrial pyruvate dehydrogenase complex \[PDC-E2\], 2-oxo-glutaric acid dehydrogenase complex)
   * Liver biopsy consistent with PBC (collected at any time prior to Screening)
2. Evidence of cirrhosis including at least one of the following:

   * Biopsy results consistent with PBC Stage 4
   * Liver stiffness as assessed by Transient Elastography (TE) Median Value ≥16.9 kilopascals (kPa)
   * Clinical evidence in the absence of acute liver failure consistent with cirrhosis including: gastroesophageal varices, ascites, radiological evidence of cirrhosis (nodular liver or enlargement of portal vein and splenomegaly)
   * Combined low platelet count (\<140,000/cubic millimeter \[mm\^3\]) with

     * persistent decrease in serum albumin, or
     * elevation in prothrombin time/international normalized ratio (INR) (not due to antithrombotic agent use), or
     * elevated bilirubin (2\*upper limit of normal \[ULN\])
3. Satisfy the criteria of the modified Child-Pugh (CP) classification for hepatic impairment during Screening:

   * Moderate: CP-B (Scores 7 to 9) or
   * Severe: CP-C (Scores 10 to 12)
4. Model of end-stage liver disease (MELD) score of 6 to 24 at Screening
5. Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥3 months) prior to Day 1, or unable to tolerate or unresponsive to UDCA (no UDCA for ≥3 months)

Exclusion Criteria:

1. Non-cirrhotic or cirrhotic CP-A (Mild; Score 5 to 6)
2. History of liver transplant or organ transplant
3. History of alcohol or drug abuse within 12 months prior to Screening
4. Hepatic encephalopathy (as defined by a West Haven score of ≥2
5. History or presence of other concomitant liver diseases including:

   * Hepatitis C virus infection and ribonucleic acid (RNA) positive
   * Active hepatitis B infection; however, participants 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
   * Alcoholic liver disease
   * Definite autoimmune liver disease or overlap hepatitis
   * Gilbert's Syndrome
6. In the opinion of the Investigator, fluctuating or rapidly deteriorating hepatic function prior to randomization

Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of Total OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Time to Maximum Concentration (Tmax) of Total OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Trough Concentration (Ctrough) of Total OCA at Week 12
timeFrame: 24 hours post-dose at Week 12
measure: Area Under the Concentration Versus Time Curve From Zero Time to 24 Hours (AUC0-24h) of Total OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Cmax of Total OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Tmax of Total OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Ctrough of Total OCA at Week 18
timeFrame: 24 hours post-dose at Week 18
measure: AUC0-24h of Total OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Cmax of Total OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Tmax of Total OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Ctrough of Total OCA at Week 24
timeFrame: 24 hours post-dose at Week 24
measure: AUC0-24h of Total OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Cmax of Total OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Tmax of Total OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Ctrough of Total OCA at Week 30
timeFrame: 24 hours post-dose at Week 30
measure: AUC0-24h of Total OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Cmax of Total OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Tmax of Total OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Ctrough of Total OCA at Week 48
timeFrame: 24 hours post-dose at Week 48
measure: AUC0-24h of Total OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Cmax of Unconjugated OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Tmax of Unconjugated OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Ctrough of Unconjugated OCA at Week 12
timeFrame: 24 hours post-dose at Week 12
measure: AUC0-24h of Unconjugated OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Cmax of Unconjugated OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Tmax of Unconjugated OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Ctrough of Unconjugated OCA at Week 18
timeFrame: 24 hours post-dose at Week 18
measure: AUC0-24h of Unconjugated OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Cmax of Unconjugated OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Tmax of Unconjugated OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Ctrough of Unconjugated OCA at Week 24
timeFrame: 24 hours post-dose at Week 24
measure: AUC0-24h of Unconjugated OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Cmax of Unconjugated OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Tmax of Unconjugated OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Ctrough of Unconjugated OCA at Week 30
timeFrame: 24 hours post-dose at Week 30
measure: AUC0-24h of Unconjugated OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Cmax of Unconjugated OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Tmax of Unconjugated OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Ctrough of Unconjugated OCA at Week 48
timeFrame: 24 hours post-dose at Week 48
measure: AUC0-24h of Unconjugated OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Cmax of Glyco Conjugate of OCA (Glyco-OCA) at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Tmax of Glyco-OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Ctrough of Glyco-OCA at Week 12
timeFrame: 24 hours post-dose at Week 12
measure: AUC0-24h of Glyco-OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Metabolite to Parent Ratio of AUC-0-24h (MRAUC) of Glyco-OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Metabolite to Parent Ratio of Cmax (MRCmax) of Glyco-OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Cmax of Glyco-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Tmax of Glyco-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Ctrough of Glyco-OCA at Week 18
timeFrame: 24 hours post-dose at Week 18
measure: AUC0-24h of Glyco-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: MRAUC of Glyco-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: MRCmax of Glyco-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Cmax of Glyco-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Tmax of Glyco-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Ctrough of Glyco-OCA at Week 24
timeFrame: 24 hours post-dose at Week 24
measure: AUC0-24h of Glyco-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: MRAUC of Glyco-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: MRCmax of Glyco-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Cmax of Glyco-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Tmax of Glyco-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Ctrough of Glyco-OCA at Week 30
timeFrame: 24 hours post-dose at Week 30
measure: AUC0-24h of Glyco-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: MRAUC of Glyco-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: MRCmax of Glyco-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Cmax of Glyco-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Tmax of Glyco-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Ctrough of Glyco-OCA at Week 48
timeFrame: 24 hours post-dose at Week 48
measure: AUC0-24h of Glyco-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: MRAUC of Glyco-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: MRCmax of Glyco-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Cmax of Tauro Conjugate of OCA (Tauro-OCA) at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Tmax of Tauro-OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Ctrough of Tauro-OCA at Week 12
timeFrame: 24 hours post-dose at Week 12
measure: AUC0-24h of Tauro-OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: MRAUC of Tauro-OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: MRCmax of Tauro-OCA at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Cmax of Tauro-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Tmax of Tauro-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Ctrough of Tauro-OCA at Week 18
timeFrame: 24 hours post-dose at Week 18
measure: AUC0-24h of Tauro-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: MRAUC of Tauro-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: MRCmax of Tauro-OCA at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Cmax of Tauro-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Tmax of Tauro-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Ctrough of Tauro-OCA at Week 24
timeFrame: 24 hours post-dose at Week 24
measure: AUC0-24h of Tauro-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: MRAUC of Tauro-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: MRCmax of Tauro-OCA at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Cmax of Tauro-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Tmax of Tauro-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Ctrough of Tauro-OCA at Week 30
timeFrame: 24 hours post-dose at Week 30
measure: AUC0-24h of Tauro-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: MRAUC of Tauro-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: MRCmax of Tauro-OCA at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Cmax of Tauro-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Tmax of Tauro-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Ctrough of Tauro-OCA at Week 48
timeFrame: 24 hours post-dose at Week 48
measure: AUC0-24h of Tauro-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: MRAUC of Tauro-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: MRCmax of Tauro-OCA at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Cmax of Glucuronide Metabolite of OCA (OCA-glucuronide) at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Tmax of OCA-glucuronide at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Ctrough of OCA-glucuronide at Week 12
timeFrame: 24 hours post-dose at Week 12
measure: AUC0-24h of OCA-glucuronide at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: MRAUC of OCA-glucuronide at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: MRCmax of OCA-glucuronide at Week 12
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
measure: Cmax of OCA-glucuronide at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Tmax of OCA-glucuronide at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Ctrough of OCA-glucuronide at Week 18
timeFrame: 24 hours post-dose at Week 18
measure: AUC0-24h of OCA-glucuronide at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: MRAUC of OCA-glucuronide at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: MRCmax of OCA-glucuronide at Week 18
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
measure: Cmax of OCA-glucuronide at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Tmax of OCA-glucuronide at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Ctrough of OCA-glucuronide at Week 24
timeFrame: 24 hours post-dose at Week 24
measure: AUC0-24h of OCA-glucuronide at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: MRAUC of OCA-glucuronide at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: MRCmax of OCA-glucuronide at Week 24
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
measure: Cmax of OCA-glucuronide at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Tmax of OCA-glucuronide at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Ctrough of OCA-glucuronide at Week 30
timeFrame: 24 hours post-dose at Week 30
measure: AUC0-24h of OCA-glucuronide at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: MRAUC of OCA-glucuronide at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: MRCmax of OCA-glucuronide at Week 30
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
measure: Cmax of OCA-glucuronide at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Tmax of OCA-glucuronide at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Ctrough of OCA-glucuronide at Week 48
timeFrame: 24 hours post-dose at Week 48
measure: AUC0-24h of OCA-glucuronide at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: MRAUC of OCA-glucuronide at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: MRCmax of OCA-glucuronide at Week 48
timeFrame: Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to approximately 3 years
Secondary outcomes:
measure: Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Number of Participants by Child-Pugh Score Component Category (Ascites Categories)
timeFrame: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)
timeFrame: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)
timeFrame: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)
timeFrame: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)
timeFrame: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Total Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Platelets at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
timeFrame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
measure: Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
timeFrame: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
measure: Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
timeFrame: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
measure: Change From Baseline in 7α-hydroxy-4-cholesten-3-one (C4) at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
timeFrame: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
measure: Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
timeFrame: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Sacramento
country: United States
facility: University of California, Ddavis Medical Center
state: California
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/ University of Miami
state: Florida
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: University Of Michigan
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Center for Liver Diseases
state: Pennsylvania
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine- Advanced Liver Therapies
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at theTexas Liver Institute
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Austral
city: Caba
country: Argentina
facility: Hospital Aleman
city: Caba
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital de Gastroenterologia "Dr Carlos Bonorino Udaondo"
city: Mendoza
country: Argentina
facility: Higea S.A.
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Kingswood
country: Australia
facility: Nepean Hospital
city: Brussels
country: Belgium
facility: CUB Hospital Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen UZA
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Belo Horizonte
country: Brazil
facility: Hospital das Clínicas da Universidade Federal de Minas Gerais - UFMG
city: Rio Grande
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: São Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig AoR
city: Bekescsaba
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz, 4. Belgyogyaszat-Gasztroenterologia-Hepatologia
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale (ASST) di Monza
state: MB
city: Modena
country: Italy
facility: AOU Ospedale Civile S. Agostino Estense - UO Medicina Metabolica
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno Klinikos
city: Klaipeda
country: Lithuania
facility: Klaipeda Seamen's Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Barcelona
country: Spain
facility: Paseo Vall d'Hebron
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe de Valencia
Study officials:
affiliation: Intercept Pharmaceuticals
name: Steven Shiff, M.D.
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.
citation: Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60(2):715-35. doi: 10.1002/hep.27210. Epub 2014 Jul 8. No abstract available.