Hepatic Impairment Trial of Obeticholic Acid

NCT01904539 | Completed Phase 1 DMC

• 1 other identifier: 747-103
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 1 study to evaluate the safety of a single 10 mg dose of obeticholic acid (OCA) in healthy volunteers and patients with liver disease.

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (4)

• Peak plasma concentration (Cmax) of OCA and conjugates

  maximum concentration

  Up to 48 hours

• Area under the concentration versus time curve from time 0 to the last sampling time with measurable analyte concentration (AUCt) of OCA and conjugates

  Post-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 216 hours post-dose

• Time to Cmax (Tmax) of OCA and conjugates

  Up to 48 hours

• Area under the concentration versus time curve from time 0-24 hours with measurable analyte concentration of OCA and conjugates. (AUC 0-24)

  24 hours

Secondary Outcomes (4)

• Urine concentration of unchanged OCA and conjugates

  0, 6, 12, 24, 30 hours

• Amount of OCA and conjugates excretion in urine

  -6to 0, 0 to 6, 6 to 12, 12 to 24, and 24 to 30 hours

• Total amount of OCA and conjugates excreted in urine

  0 to 30 hours

• Protein Binding

  0, 0.75, 1.5, 6, and 24 hours

Study Arms (4)

Healthy Volunteer

EXPERIMENTAL

Healthy volunteers receiving a single dose of obeticholic acid 10 mg.

Drug: obeticholic acid 10 mg

Mild Hepatic Impairment

EXPERIMENTAL

Subjects with mild hepatic impairment defined as Child-Pugh class A receiving a single dose of obeticholic acid 10mg.

Drug: obeticholic acid 10 mg

Moderate Hepatic Impairment

EXPERIMENTAL

Subjects with moderate hepatic impairment defined as Child-Pugh class B receiving obeticholic acid 10mg.

Drug: obeticholic acid 10 mg

Severe Hepatic Impairment

EXPERIMENTAL

Subjects with severe hepatic impairment defined as Child-Pugh class C receiving obeticholic acid 10 mg.

Drug: obeticholic acid 10 mg

Interventions

obeticholic acid 10 mg DRUG

Single dose OCA 10mg in each arm

Also known as: INT-747, 6α-ethyl chenodeoxycholic acid, 6-ECDCA

Healthy Volunteer; Mild Hepatic Impairment; Moderate Hepatic Impairment; Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male subjects ≥ 18 years of age
• Subjects will have a minimum body weight of 45 kg or body mass index (BMI)\> 18 kg/m2.
• Contraception: Female subjects must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use ≥ 1 effective method of contraception during the trial and until at least 30 days after administration of OCA.
• Subjects must provide written informed consent and agree to comply with the trial protocol.
• Subjects with Hepatic Impairment:
• Evidence of hepatic disease
• Score ≥ 2 on one of the Child-Pugh parameters, or
• Histological diagnosis of cirrhosis or presence of esophageal varices, or
• Abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) levels
• Subjects will satisfy the criteria of the modified Child-Pugh classification for hepatic impairment during Screening:
• Mild hepatic impairment: Class A (Child-Pugh Scores 5-6 points)
• Moderate hepatic impairment: Class B (Child-Pugh Scores 7-9 points)
• Severe hepatic impairment: Class C (Child Pugh Scores 10-15 points)
• Healthy volunteers:
• Absence of clinically-relevant abnormalities identified by a detailed medical history, full physical examination, 12-lead ECG

You may not qualify if:

• Positive test for human immunodeficiency virus (HIV)-1 or HIV-2 at screening
• Presence or history of malignancy, with the exception of basal cell carcinoma
• Received an investigational drug, including OCA, within 30 days or t½=5 prior to dosing
• Blood or plasma donation within 30 days prior to dosing
• History of non-compliance to medical regimens, or subjects who are considered to be potentially unreliable
• Presence or history of clinically significant cardiac arrhythmias that may prohibit the subject from participating in the trial
• Female subjects who are pregnant or lactating
• Subjects who have irritable bowel disease or other GI disorders that have the potential to alter drug or bile acid absorption.
• Subjects who have a history of gall bladder removal, gastric bypass or other GI surgery that may affect drug absorption or the enterohepatic circulation.
• Subjects with Hepatic Impairment
• History of alcohol or drug abuse 3 months prior to dosing
• In the opinion of the Investigator and medical monitor, fluctuating or rapidly deteriorating hepatic function within the screening period
• In the opinion of the Investigator, any evidence of additional severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding likely to affect the conduct of the trial or interpretation of the data
• Subjects who have a transjugular intrahepatic portosystemic shunt and/or have undergone portacaval shunting
• Subjects with Wilson's disease, alpha-1 antitrypsin deficiency, glycogen storage diseases and galactosemia

Sponsors & Collaborators

• Intercept Pharmaceuticals: lead

Study Sites (2)

Clinical Pharmacology of Miami, Inc.

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• Edwards JE, LaCerte C, Peyret T, Gosselin NH, Marier JF, Hofmann AF, Shapiro D. Modeling and Experimental Studies of Obeticholic Acid Exposure and the Impact of Cirrhosis Stage. Clin Transl Sci. 2016 Dec;9(6):328-336. doi: 10.1111/cts.12421. Epub 2016 Oct 15.

  PMID: 27743502 DERIVED

MeSH Terms

Interventions

obeticholic acid

Study Officials

• David Shapiro, MD

  Intercept Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2013
• First Posted: July 22, 2013
• Study Start: June 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 24, 2013

Record last verified: 2013-10

Locations

US (2)