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Hepatic Impairment Trial of Obeticholic Acid

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ClinicalTrials.gov Identifier: NCT01904539
Recruitment Status : Completed
First Posted : July 22, 2013
Last Update Posted : October 24, 2013
Sponsor:
Information provided by (Responsible Party):
Intercept Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 23, 2013
First Posted Date  ICMJE July 22, 2013
Last Update Posted Date October 24, 2013
Study Start Date  ICMJE June 2013
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2013)
  • Peak plasma concentration (Cmax) of OCA and conjugates [ Time Frame: Up to 48 hours ]
    maximum concentration
  • Area under the concentration versus time curve from time 0 to the last sampling time with measurable analyte concentration (AUCt) of OCA and conjugates [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 24 hours ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2013)
  • Urine concentration of unchanged OCA and conjugates [ Time Frame: 0, 6, 12, 24, 30 hours ]
  • Amount of OCA and conjugates excretion in urine [ Time Frame: -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 [ Time Frame: 0 to 30 hours ]
  • Protein Binding [ Time Frame: 0, 0.75, 1.5, 6, and 24 hours ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hepatic Impairment Trial of Obeticholic Acid
Official Title  ICMJE An Open-Label, Single-Dose Trial to Assess the Effects of Hepatic Impairment on the Pharmacokinetics of Obeticholic Acid (OCA)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Hepatic Impairment
Intervention  ICMJE Drug: obeticholic acid 10 mg
Single dose OCA 10mg in each arm
Other Names:
  • INT-747
  • 6α-ethyl chenodeoxycholic acid
  • 6-ECDCA
Study Arms  ICMJE
  • Experimental: Healthy Volunteer
    Healthy volunteers receiving a single dose of obeticholic acid 10 mg.
    Intervention: Drug: obeticholic acid 10 mg
  • Experimental: Mild Hepatic Impairment
    Subjects with mild hepatic impairment defined as Child-Pugh class A receiving a single dose of obeticholic acid 10mg.
    Intervention: Drug: obeticholic acid 10 mg
  • Experimental: Moderate Hepatic Impairment
    Subjects with moderate hepatic impairment defined as Child-Pugh class B receiving obeticholic acid 10mg.
    Intervention: Drug: obeticholic acid 10 mg
  • Experimental: Severe Hepatic Impairment
    Subjects with severe hepatic impairment defined as Child-Pugh class C receiving obeticholic acid 10 mg.
    Intervention: Drug: obeticholic acid 10 mg
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 17, 2013)
32
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Subject Inclusion Criteria All Subjects

  • 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

    1. Score ≥ 2 on one of the Child-Pugh parameters, or
    2. Histological diagnosis of cirrhosis or presence of esophageal varices, or
    3. 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:

    1. Mild hepatic impairment: Class A (Child-Pugh Scores 5-6 points)
    2. Moderate hepatic impairment: Class B (Child-Pugh Scores 7-9 points)
    3. 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
  • Clinical laboratory tests within the normal reference range
  • Subjects must be within ± 10 years of the mean age and within 20% of the mean BMI of the hepatic impaired subjects (Child-Pugh category A, B, and C)

Subject Exclusion Criteria All Subjects

  • 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
  • Heavy smoker or use of tobacco or nicotine products

Healthy Volunteers

  • Presence of significant uncontrolled disease that will complicate execution of the trial or interfere with the absorption, distribution, metabolism, or excretion of drugs via the gut
  • Evidence of chronic or acute liver disease as documented by medical history, physical examination or diagnostic tests that it likely to affect the conduct of the trial or interpretation of the data
  • History of and/or current alcohol abuse (defined as consumption of more than 210 mL of alcohol per week; or the equivalent of fourteen 4-oz glasses of wine, or fourteen 12-oz cans/bottles of beer or wine coolers per week) or drug abuse within the prior two years
  • Smoke or use tobacco or nicotine products
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01904539
Other Study ID Numbers  ICMJE 747-103
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Intercept Pharmaceuticals
Study Sponsor  ICMJE Intercept Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Shapiro, MD Intercept Pharmaceuticals
PRS Account Intercept Pharmaceuticals
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP