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Liver Cirrhosis, BiliaryPhase 4NCT03633227

Study of Obeticholic Acid (OCA) Evaluating Pharmacokinetics and Safety in Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment

A Phase 4 study testing Obeticholic Acid (OCA) in people with Liver Cirrhosis, Biliary, run by Intercept Pharmaceuticals at 40 sites in 12 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Liver Cirrhosis, Biliary
What is being tested?
Obeticholic Acid (OCA)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
22 participants
Where
40 sitesin 12 countries
Study dates
22 Jun 2018to 9 Jul 2021
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • Evidence of cirrhosis including at least one of the following:
  • Biopsy results consistent with PBC Stage 4
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  • 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])
  • 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)
  • Model of end-stage liver disease (MELD) score of 6 to 24 at Screening
  • 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)

Who cannot join

  • Non-cirrhotic or cirrhotic CP-A (Mild; Score 5 to 6)
  • History of liver transplant or organ transplant
  • History of alcohol or drug abuse within 12 months prior to Screening
  • Hepatic encephalopathy (as defined by a West Haven score of ≥2
  • History or presence of other concomitant liver diseases including:
  • Hepatitis C virus infection and ribonucleic acid (RNA) positive
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  • 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
  • In the opinion of the Investigator, fluctuating or rapidly deteriorating hepatic function prior to randomization
  • Other inclusion/exclusion criteria may apply.

Trial locations and contacts

40 sites in 12 countries.

40 sites in 12 countries

United States11 sites

  • University Of Michigan

    Ann Arbor, Michigan, 48109

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • The Liver Institute at Methodist Dallas Medical Center

    Dallas, Texas, 75203

  • Baylor College of Medicine- Advanced Liver Therapies

    Houston, Texas, 77030

  • Kansas City Research Institute

    Kansas City, Missouri, 64131

  • Schiff Center for Liver Diseases/ University of Miami

    Miami, Florida, 33136

  • UPMC Center for Liver Diseases

    Pittsburgh, Pennsylvania, 15213

  • Inland Empire Liver Foundation

    Rialto, California, 92377

  • University of California, Ddavis Medical Center

    Sacramento, California, 95817

  • American Research Corporation at theTexas Liver Institute

    San Antonio, Texas, 78215

Other trials in United States

Argentina8 sites

  • Hospital Italiano de Buenos Aires

    Buenos Aires

  • Hospital Universitario Austral

    Buenos Aires

  • Hospital Aleman

    Caba

  • Hospital Britanico de Buenos Aires

    Caba

  • Hospital de Gastroenterologia "Dr Carlos Bonorino Udaondo"

    Ciudad Autonoma de Buenos Aire

  • Higea S.A.

    Mendoza, M5500DPS

  • Hospital Universitario Austral

    Pilar

  • Hospital Provincial del Centenario

    Rosario

Other trials in Argentina

Belgium3 sites

  • CUB Hospital Erasme

    Brussels, 1070

  • Universitair Ziekenhuis Antwerpen UZA

    Edegem

  • University Hospital Leuven

    Leuven, 3000

Other trials in Belgium

Brazil3 sites

  • Hospital das Clínicas da Universidade Federal de Minas Gerais - UFMG

    Belo Horizonte

  • Hospital de Clinicas de Porto Alegre

    Rio Grande

  • Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo

    São Paulo, 054003-000

Other trials in Brazil

Lithuania3 sites

  • Hospital of Lithuanian University of Health Sciences Kauno Klinikos

    Kaunas

  • Klaipeda Seamen's Hospital

    Klaipėda, LT-92288

  • Vilnius University Hospital Santaros Klinikos

    Vilnius

Other trials in Lithuania

Spain3 sites

  • Paseo Vall d'Hebron

    Barcelona, 8035

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Universitari I Politecnic La Fe de Valencia

    Valencia, 46026

Other trials in Spain

Australia2 sites

  • Royal Prince Alfred Hospital

    Camperdown, 2050

  • Nepean Hospital

    Kingswood, 2747

Other trials in Australia

Estonia2 sites

  • West Tallinn Central Hospital

    Tallinn, 10617

  • Tartu University Hospital

    Tartu

Other trials in Estonia

Italy2 sites

  • AOU Ospedale Civile S. Agostino Estense - UO Medicina Metabolica

    Modena, 41126

  • Azienda Socio Sanitaria Territoriale (ASST) di Monza

    Monza, MB, 20900

Other trials in Italy

Canada1 site

  • Toronto General Hospital

    Toronto

Other trials in Canada

Germany1 site

  • Universitatsklinikum Leipzig AoR

    Leipzig, 04103

Other trials in Germany

Hungary1 site

  • Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz, 4. Belgyogyaszat-Gasztroenterologia-Hepatologia

    Békéscsaba

Other trials in Hungary

About this study

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

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.

Being tested
Obeticholic Acid (OCA), Placebo
Keywords
Primary Biliary Cholangitis, Primary Biliary Cirrhosis, PBC, Hepatic Impairment, Cirrhosis, Liver
Medical subject headings
Liver Cirrhosis, Biliary, Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Obeticholic Acid (OCA)Drug

    Also called 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747

    OCA will be administered per dose and schedule specified in the arm description.

  • PlaceboDrug

    OCA matching placebo will be administered per the schedule specified in the arm description.

Study groups in NCT03633227
Study groupRoleWhat they receive
Obeticholic Acid (OCA)ExperimentalParticipants will initiate treatment with OCA 5 milligrams (mg) tablets orally once weekly. At Week 12, if there are no safety concerns, the dose will be up-titrated to OCA 5 mg twice weekly. Every 6 weeks thereafter, based on tolerability assessments, further up-titration of dose will be considered. At each titration visit, the participants will start the higher dose regimen no earlier than 2 days after the prior dose. The maximum dose titration will be OCA 10 mg twice weekly at least 3 days apart. The minimum treatment duration will be 48-weeks. Participants, who complete their 48-week treatment, can continue the treatment until all randomized participants complete their 48-week treatment period and the database for that period is locked (total duration: approximately up to 3 years).
Receives: Drug: Obeticholic Acid (OCA)
PlaceboPlacebo comparatorParticipants will receive OCA matching placebo orally once weekly or twice weekly for the duration of at least 48-weeks. Participants, who complete their 48-week treatment, can continue the treatment until all randomized participants complete their 48-week treatment period and the database for that period is locked (total duration: approximately up to 3 years).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Observed Concentration (Cmax) of Total OCA at Week 12

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. Pharmacokinetics (PK) of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.

    Measured: 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

  2. Time to Maximum Concentration (Tmax) of Total OCA at Week 12

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  3. Trough Concentration (Ctrough) of Total OCA at Week 12

    Ctrough was considered as the concentration at 24-hours post-dose at Week 12. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 24 hours post-dose at Week 12

  4. Area Under the Concentration Versus Time Curve From Zero Time to 24 Hours (AUC0-24h) of Total OCA at Week 12

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  5. Cmax of Total OCA at Week 18

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  6. Tmax of Total OCA at Week 18

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  7. Ctrough of Total OCA at Week 18

    Ctrough was considered as the concentration at 24-hours post-dose at Week 18. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 24 hours post-dose at Week 18

  8. AUC0-24h of Total OCA at Week 18

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  9. Cmax of Total OCA at Week 24

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  10. Tmax of Total OCA at Week 24

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  11. Ctrough of Total OCA at Week 24

    Ctrough was considered as the concentration at 24-hours post-dose at Week 24. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 24 hours post-dose at Week 24

  12. AUC0-24h of Total OCA at Week 24

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  13. Cmax of Total OCA at Week 30

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  14. Tmax of Total OCA at Week 30

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  15. Ctrough of Total OCA at Week 30

    Ctrough was considered as the concentration at 24-hours post-dose at Week 30. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 24 hours post-dose at Week 30

  16. AUC0-24h of Total OCA at Week 30

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  17. Cmax of Total OCA at Week 48

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  18. Tmax of Total OCA at Week 48

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 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

  19. Ctrough of Total OCA at Week 48

    Ctrough was considered as the concentration at 24-hours post-dose at Week 48. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.

    Measured: 24 hours post-dose at Week 48

  20. AUC0-24h of Total OCA at Week 48

    Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  21. Cmax of Unconjugated OCA at Week 12

    Measured: 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

  22. Tmax of Unconjugated OCA at Week 12

    Measured: 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

  23. Ctrough of Unconjugated OCA at Week 12

    Ctrough was considered as the concentration at 24-hours post-dose at Week 12.

    Measured: 24 hours post-dose at Week 12

  24. AUC0-24h of Unconjugated OCA at Week 12

    AUC0-24 was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  25. Cmax of Unconjugated OCA at Week 18

    Measured: 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

  26. Tmax of Unconjugated OCA at Week 18

    Measured: 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

  27. Ctrough of Unconjugated OCA at Week 18

    Ctrough was considered as the concentration at 24-hours post-dose at Week 18.

    Measured: 24 hours post-dose at Week 18

  28. AUC0-24h of Unconjugated OCA at Week 18

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  29. Cmax of Unconjugated OCA at Week 24

    Measured: 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

  30. Tmax of Unconjugated OCA at Week 24

    Measured: 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

  31. Ctrough of Unconjugated OCA at Week 24

    Ctrough was considered as the concentration at 24-hours post-dose at Week 24.

    Measured: 24 hours post-dose at Week 24

  32. AUC0-24h of Unconjugated OCA at Week 24

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  33. Cmax of Unconjugated OCA at Week 30

    Measured: 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

  34. Tmax of Unconjugated OCA at Week 30

    Measured: 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

  35. Ctrough of Unconjugated OCA at Week 30

    Ctrough was considered as the concentration at 24-hours post-dose at Week 30.

    Measured: 24 hours post-dose at Week 30

  36. AUC0-24h of Unconjugated OCA at Week 30

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  37. Cmax of Unconjugated OCA at Week 48

    Measured: 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

  38. Tmax of Unconjugated OCA at Week 48

    Measured: 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

  39. Ctrough of Unconjugated OCA at Week 48

    Ctrough was considered as the concentration at 24-hours post-dose at Week 48.

    Measured: 24 hours post-dose at Week 48

  40. AUC0-24h of Unconjugated OCA at Week 48

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  41. Cmax of Glyco Conjugate of OCA (Glyco-OCA) at Week 12

    Measured: 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

  42. Tmax of Glyco-OCA at Week 12

    Measured: 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

  43. Ctrough of Glyco-OCA at Week 12

    Ctrough was considered as the concentration at 24-hours post-dose at Week 12.

    Measured: 24 hours post-dose at Week 12

  44. AUC0-24h of Glyco-OCA at Week 12

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  45. Metabolite to Parent Ratio of AUC-0-24h (MRAUC) of Glyco-OCA at Week 12

    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  46. Metabolite to Parent Ratio of Cmax (MRCmax) of Glyco-OCA at Week 12

    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  47. Cmax of Glyco-OCA at Week 18

    Measured: 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

  48. Tmax of Glyco-OCA at Week 18

    Measured: 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

  49. Ctrough of Glyco-OCA at Week 18

    Ctrough was considered as the concentration at 24-hours post-dose at Week 18.

    Measured: 24 hours post-dose at Week 18

  50. AUC0-24h of Glyco-OCA at Week 18

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  51. MRAUC of Glyco-OCA at Week 18

    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  52. MRCmax of Glyco-OCA at Week 18

    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  53. Cmax of Glyco-OCA at Week 24

    Measured: 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

  54. Tmax of Glyco-OCA at Week 24

    Measured: 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

  55. Ctrough of Glyco-OCA at Week 24

    Ctrough was considered as the concentration at 24-hours post-dose at Week 24.

    Measured: 24 hours post-dose at Week 24

  56. AUC0-24h of Glyco-OCA at Week 24

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  57. MRAUC of Glyco-OCA at Week 24

    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  58. MRCmax of Glyco-OCA at Week 24

    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  59. Cmax of Glyco-OCA at Week 30

    Measured: 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

  60. Tmax of Glyco-OCA at Week 30

    Measured: 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

  61. Ctrough of Glyco-OCA at Week 30

    Ctrough was considered as the concentration at 24-hours post-dose at Week 30.

    Measured: 24 hours post-dose at Week 30

  62. AUC0-24h of Glyco-OCA at Week 30

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  63. MRAUC of Glyco-OCA at Week 30

    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  64. MRCmax of Glyco-OCA at Week 30

    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  65. Cmax of Glyco-OCA at Week 48

    Measured: 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

  66. Tmax of Glyco-OCA at Week 48

    Measured: 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

  67. Ctrough of Glyco-OCA at Week 48

    Ctrough was considered as the concentration at 24-hours post-dose at Week 48.

    Measured: 24 hours post-dose at Week 48

  68. AUC0-24h of Glyco-OCA at Week 48

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  69. MRAUC of Glyco-OCA at Week 48

    MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  70. MRCmax of Glyco-OCA at Week 48

    MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  71. Cmax of Tauro Conjugate of OCA (Tauro-OCA) at Week 12

    Measured: 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

  72. Tmax of Tauro-OCA at Week 12

    Measured: 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

  73. Ctrough of Tauro-OCA at Week 12

    Ctrough was considered as the concentration at 24-hours post-dose at Week 12.

    Measured: 24 hours post-dose at Week 12

  74. AUC0-24h of Tauro-OCA at Week 12

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  75. MRAUC of Tauro-OCA at Week 12

    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  76. MRCmax of Tauro-OCA at Week 12

    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  77. Cmax of Tauro-OCA at Week 18

    Measured: 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

  78. Tmax of Tauro-OCA at Week 18

    Measured: 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

  79. Ctrough of Tauro-OCA at Week 18

    Ctrough was considered as the concentration at 24-hours post-dose at Week 18.

    Measured: 24 hours post-dose at Week 18

  80. AUC0-24h of Tauro-OCA at Week 18

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  81. MRAUC of Tauro-OCA at Week 18

    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  82. MRCmax of Tauro-OCA at Week 18

    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  83. Cmax of Tauro-OCA at Week 24

    Measured: 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

  84. Tmax of Tauro-OCA at Week 24

    Measured: 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

  85. Ctrough of Tauro-OCA at Week 24

    Ctrough was considered as the concentration at 24-hours post-dose at Week 24.

    Measured: 24 hours post-dose at Week 24

  86. AUC0-24h of Tauro-OCA at Week 24

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  87. MRAUC of Tauro-OCA at Week 24

    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  88. MRCmax of Tauro-OCA at Week 24

    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  89. Cmax of Tauro-OCA at Week 30

    Measured: 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

  90. Tmax of Tauro-OCA at Week 30

    Measured: 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

  91. Ctrough of Tauro-OCA at Week 30

    Ctrough was considered as the concentration at 24-hours post-dose at Week 30.

    Measured: 24 hours post-dose at Week 30

  92. AUC0-24h of Tauro-OCA at Week 30

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  93. MRAUC of Tauro-OCA at Week 30

    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  94. MRCmax of Tauro-OCA at Week 30

    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  95. Cmax of Tauro-OCA at Week 48

    Measured: 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

  96. Tmax of Tauro-OCA at Week 48

    Measured: 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

  97. Ctrough of Tauro-OCA at Week 48

    Ctrough was considered as the concentration at 24-hours post-dose at Week 48.

    Measured: 24 hours post-dose at Week 48

  98. AUC0-24h of Tauro-OCA at Week 48

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  99. MRAUC of Tauro-OCA at Week 48

    MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  100. MRCmax of Tauro-OCA at Week 48

    MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.

    Measured: 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

  101. Cmax of Glucuronide Metabolite of OCA (OCA-glucuronide) at Week 12

    Measured: 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

  102. Tmax of OCA-glucuronide at Week 12

    Measured: 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

  103. Ctrough of OCA-glucuronide at Week 12

    Ctrough was considered as the concentration at 24-hours post-dose at Week 12.

    Measured: 24 hours post-dose at Week 12

  104. AUC0-24h of OCA-glucuronide at Week 12

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  105. MRAUC of OCA-glucuronide at Week 12

    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  106. MRCmax of OCA-glucuronide at Week 12

    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.

    Measured: 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

  107. Cmax of OCA-glucuronide at Week 18

    Measured: 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

  108. Tmax of OCA-glucuronide at Week 18

    Measured: 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

  109. Ctrough of OCA-glucuronide at Week 18

    Ctrough was considered as the concentration at 24-hours post-dose at Week 18.

    Measured: 24 hours post-dose at Week 18

  110. AUC0-24h of OCA-glucuronide at Week 18

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  111. MRAUC of OCA-glucuronide at Week 18

    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  112. MRCmax of OCA-glucuronide at Week 18

    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.

    Measured: 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

  113. Cmax of OCA-glucuronide at Week 24

    Measured: 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

  114. Tmax of OCA-glucuronide at Week 24

    Measured: 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

  115. Ctrough of OCA-glucuronide at Week 24

    Ctrough was considered as the concentration at 24-hours post-dose at Week 24.

    Measured: 24 hours post-dose at Week 24

  116. AUC0-24h of OCA-glucuronide at Week 24

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  117. MRAUC of OCA-glucuronide at Week 24

    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  118. MRCmax of OCA-glucuronide at Week 24

    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.

    Measured: 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

  119. Cmax of OCA-glucuronide at Week 30

    Measured: 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

  120. Tmax of OCA-glucuronide at Week 30

    Measured: 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

  121. Ctrough of OCA-glucuronide at Week 30

    Ctrough was considered as the concentration at 24-hours post-dose at Week 30.

    Measured: 24 hours post-dose at Week 30

  122. AUC0-24h of OCA-glucuronide at Week 30

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  123. MRAUC of OCA-glucuronide at Week 30

    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  124. MRCmax of OCA-glucuronide at Week 30

    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.

    Measured: 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

  125. Cmax of OCA-glucuronide at Week 48

    Measured: 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

  126. Tmax of OCA-glucuronide at Week 48

    Measured: 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

  127. Ctrough of OCA-glucuronide at Week 48

    Ctrough was considered as the concentration at 24-hours post-dose at Week 48.

    Measured: 24 hours post-dose at Week 48

  128. AUC0-24h of OCA-glucuronide at Week 48

    AUC0-24h was calculated using the linear/linear trapezoidal rule.

    Measured: 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

  129. MRAUC of OCA-glucuronide at Week 48

    MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.

    Measured: 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

  130. MRCmax of OCA-glucuronide at Week 48

    MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.

    Measured: 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

  131. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.

    An SAE was any AE that results in death, was life-threatening, resulted in a persistent or significant disability/incapacity, resulted in in-patient hospitalization or prolonged an existing hospitalization, was a congenital anomaly/birth defect, or was an important medical event that could jeopardize the participant or could have required medical intervention to prevent one of the outcomes listed above.

    TEAE was defined as any AE if it met one or more of the following criteria: 1) An AE started on or after the first study drug dose and within 30 days after the last dose of study drug, 2) An AE occurred prior to the first study drug dose that worsens (increase in grade) after the first study drug dose.

    Measured: Baseline up to approximately 3 years

Secondary outcomes (22)

  1. 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

    The MELD scoring system is used to assess the severity of chronic liver disease. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and prothrombin international normalized ratio (INR): 3.78×log normal (ln) [total bilirubin (mg/deciliter [dL])] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  2. 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

    The MELD-Na scoring system is used to assess the severity of chronic liver disease in the participants with an initial MELD(i) score greater than 11. MELD-Na score is derived from the participant's serum total bilirubin, serum creatinine, INR, and sodium. The MELD-Na score is re-calculated as follows:

    MELD-Na = MELD(i) + 1.32*(137-Na) - [0.033*MELD(i)*(137-Na)]. MELD score ranges from 6-40 with higher scores indicating more severe liver disease and a worse outcome.

    The MELD(i) score is derived from the participant's serum total bilirubin, serum creatinine, and prothrombin international normalized ratio (INR): 3.78×log normal (ln) [total bilirubin (mg/deciliter [dL])] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  3. 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

    The Child-Pugh classification was a scoring system used for the classification of the severity of cirrhosis. It included three continuous variables (bilirubin, albumin, and INR) and two discrete variables (ascites and encephalopathy). Each variable was scored 1-3 with 3 indicating most severe derangement. The determination of Child-Pugh score ranged from 5 to 15. The higher the score, the sicker the participant.

    Measured: Baseline, Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15

  4. Number of Participants by Child-Pugh Score Component Category (Ascites Categories)

    Number of participants with Child-Pugh component - ascites categories of none, mild, and moderate-severe has been reported. The ascites categories were defined per investigator's discretion.

    Measured: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15

  5. Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)

    Number of participants with Child-Pugh component - prothrombin time (measured as INR) in categories of <1.7, 1.7 - 2.3, and >2.3 has been reported.

    Measured: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15

  6. Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)

    Number of participants with Child-Pugh component - serum albumin levels in categories of >35 gram per liter (g/L), 28-35 g/L, or <28 g/L has been reported.

    Measured: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15

  7. Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)

    Number of participants with Child-Pugh component - total bilirubin levels in categories of <34 micromole per liter (µmol/L), 34-50 µmol/L, and >50 µmol/L has been reported.

    Measured: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15

  8. Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)

    Number of participants with Child-Pugh component - Hepatic encephalopathy in categories of Grade 0, Grade 1 or 2, and Grade 3 and 4 has been reported.

    Grade 0: normal consciousness, normal personality, normal neurological examination, normal electroencephalogram.

    Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles, per second (cps) waves.

    Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves.

    Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves.

    Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cps delta activity.

    Measured: Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15

  9. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  10. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  11. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  12. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  13. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  14. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  15. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  16. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  17. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  18. 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

    Measured: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15

  19. Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

    Total bile acids (micromole [μM]) = total ursodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total cholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM.

    Measured: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

  20. Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

    Total endogenous bile acids (μM) = total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total cholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in μM.

    Measured: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

  21. 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

    Measured: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

  22. 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

    Measured: Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2018
  2. Study start22 Jun 2018
  3. Primary completion9 Jul 2021
  4. Study completion9 Jul 2021

Why it stopped: Due to Ocaliva (obeticholic acid) US labeling update, the sponsor decided to terminate the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03633227
Sponsor's protocol ID
747-401
Status last verified
Aug 2022
First submitted
8 Apr 2018
Last updated
6 Sep 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 19554543

  • 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.

    PubMed 19501929

  • 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.

    PubMed 25042402

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Obeticholic Acid (OCA) in people with Liver Cirrhosis, Biliary, run by Intercept Pharmaceuticals at 40 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Argentina, Belgium, Brazil, Lithuania and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Concentration (Cmax) of Total OCA at Week 12 (time frame: 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). The study lists 131 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03633227, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2022.

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