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

I

Intercept Pharmaceuticals

Status and phase

Terminated
Phase 4

Conditions

Liver Cirrhosis, Biliary

Treatments

Drug: Placebo
Drug: Obeticholic Acid (OCA)

Study type

Interventional

Funder types

Industry

Identifiers

NCT03633227
747-401

Details and patient eligibility

About

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.

Enrollment

22 patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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
  • 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)

Exclusion criteria

  • 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
  • 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 design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

22 participants in 2 patient groups, including a placebo group

Obeticholic Acid (OCA)
Experimental group
Description:
Participants 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).
Treatment:
Drug: Obeticholic Acid (OCA)
Placebo
Placebo Comparator group
Description:
Participants 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).
Treatment:
Drug: Placebo

Trial documents
2

Trial contacts and locations

40

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Data sourced from clinicaltrials.gov

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