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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

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.

Condition or disease Intervention/treatment Phase
Hepatic Impairment Drug: obeticholic acid 10 mg Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: An Open-Label, Single-Dose Trial to Assess the Effects of Hepatic Impairment on the Pharmacokinetics of Obeticholic Acid (OCA)
Study Start Date : June 2013
Actual Primary Completion Date : October 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Healthy Volunteer
Healthy volunteers receiving a single dose of obeticholic acid 10 mg.
Drug: obeticholic acid 10 mg
Single dose OCA 10mg in each arm
Other Names:
  • INT-747
  • 6α-ethyl chenodeoxycholic acid
  • 6-ECDCA

Experimental: Mild Hepatic Impairment
Subjects with mild hepatic impairment defined as Child-Pugh class A receiving a single dose of obeticholic acid 10mg.
Drug: obeticholic acid 10 mg
Single dose OCA 10mg in each arm
Other Names:
  • INT-747
  • 6α-ethyl chenodeoxycholic acid
  • 6-ECDCA

Experimental: Moderate Hepatic Impairment
Subjects with moderate hepatic impairment defined as Child-Pugh class B receiving obeticholic acid 10mg.
Drug: obeticholic acid 10 mg
Single dose OCA 10mg in each arm
Other Names:
  • INT-747
  • 6α-ethyl chenodeoxycholic acid
  • 6-ECDCA

Experimental: Severe Hepatic Impairment
Subjects with severe hepatic impairment defined as Child-Pugh class C receiving obeticholic acid 10 mg.
Drug: obeticholic acid 10 mg
Single dose OCA 10mg in each arm
Other Names:
  • INT-747
  • 6α-ethyl chenodeoxycholic acid
  • 6-ECDCA




Primary Outcome Measures :
  1. Peak plasma concentration (Cmax) of OCA and conjugates [ Time Frame: Up to 48 hours ]
    maximum concentration

  2. 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 ]
  3. Time to Cmax (Tmax) of OCA and conjugates [ Time Frame: Up to 48 hours ]
  4. 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 ]

Secondary Outcome Measures :
  1. Urine concentration of unchanged OCA and conjugates [ Time Frame: 0, 6, 12, 24, 30 hours ]
  2. 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 ]
  3. Total amount of OCA and conjugates excreted in urine [ Time Frame: 0 to 30 hours ]
  4. Protein Binding [ Time Frame: 0, 0.75, 1.5, 6, and 24 hours ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01904539


Locations
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United States, Florida
Clinical Pharmacology of Miami, Inc.
Miami, Florida, United States, 33014
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
Sponsors and Collaborators
Intercept Pharmaceuticals
Investigators
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Study Director: David Shapiro, MD Intercept Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Intercept Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01904539     History of Changes
Other Study ID Numbers: 747-103
First Posted: July 22, 2013    Key Record Dates
Last Update Posted: October 24, 2013
Last Verified: October 2013

Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases
Chenodeoxycholic Acid
Cathartics
Gastrointestinal Agents