Effect of Food on Pharmacokinetics of Obeticholic Acid (OCA)

Study Overview
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Brief Summary
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This is an open label, randomized, balanced, single center, single dose, trial to assess the pharmacokinetic (PK) profile of OCA, glyco-OCA and tauro-OCA on an empty stomach (fasted condition) and following a high fat, high calorie meal (fed condition) in a 2-period, 2-sequence, crossover manner.

Official Title
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An Open Label Trial to Assess the Effects of Food on the Pharmacokinetic Parameters of Obeticholic Acid (OCA)

Conditions
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Healthy

Intervention / Treatment
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* Drug: OCA 10 mg
* Drug: OCA 25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are required to meet the following criteria in order to be included in the trial. Male or female subjects from 18 to 55 years Contraception: Female subjects must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use more than 1 effective (≤ 1% failure rate) method of contraception during the trial and until at least 30 days after the last dose of OCA. Effective methods of contraception are considered to be: Double barrier method, ie, (a) condom (male or female) with spermicide or (b) diaphragm with spermicide Intrauterine device (IUD) Vasectomy Good general health as determined by medical history, and by results of physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory tests obtained within 14 days prior to Day 0 Body mass index (BMI) of 18 to 28; BMI is determined by the following equation: BMI = weight/height2 (kg/m2). Willing to abstain from alcohol, caffeine, and xanthine-containing food and beverages for 72 hours prior to each period check in and during participation of the inpatient periods of the trial Willing and able to give written informed consent Exclusion Criteria: Subjects meeting the following criteria will be excluded from the trial. Prior participation in a clinical trial of OCA (INT-747; 6-ECDCA) History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the large intestine, eg, inflammatory bowel disease History of gastrointestinal surgeries or gall bladder removal (cholecystectomy) History or presence of a clinically significant cardiovascular, hepatic, diabetic, gastrointestinal, metabolic, neurologic, pulmonary, endocrine, psychiatric, or neoplastic disorder(s) History of known or suspected clinically significant hypersensitivity to any drug, aside from penicillin Ingestion of a prescription medication within 14 days prior to Day 0 or ingestion of an over the counter medication within 7 days prior to Day 0 Participation in radiologic examinations involving parenteral administration of iodinated contrast materials within 2 weeks prior to screening, or subsequently, through the end of trial participation History or presence of alcohol abuse (defined as consumption of more than 210 mL of alcohol per week; or the equivalent of fourteen 4 ounces (oz) glasses of wine, or fourteen 12 oz cans/bottles of beer or wine coolers per week) History or presence of substance abuse within the past 2 years or positive drug screen tests Smoker or user of tobacco or nicotine products Any screening laboratory test for which the results are not within the normal reference range and considered clinically significant Participation in another investigational drug trial within 30 days prior to Day 0 History of noncompliance to medical regimens, or subjects who are considered to be potentially unreliable Blood or plasma donation within 30 days prior to Day 0 Mental instability or incompetence Presence of human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OCA 10 mg while fasted<br>OCA 10 mg orally in the fasting state | Drug: OCA 10 mg<br>* OCA 10 mg tablet oral<br>* Other names: 6α-ethyl chenodeoxycholic acid;(6-ECDCA), INT-747;|
| Experimental: OCA 10 mg while Fed<br>OCA 10 mg orally in the fed state | Drug: OCA 10 mg<br>* OCA 10 mg tablet oral<br>* Other names: 6α-ethyl chenodeoxycholic acid;(6-ECDCA), INT-747;|
| Experimental: OCA 25 mg while fasted<br>OCA 25 mg orally in the fasting state | Drug: OCA 25 mg<br>* OCA 25 mg tablet oral<br>* Other names: 6α-ethyl chenodeoxycholic acid;(6-ECDCA), INT-747;|
| Experimental: OCA 25 mg while Fed<br>OCA 25 mg orally in the fed state | Drug: OCA 25 mg<br>* OCA 25 mg tablet oral<br>* Other names: 6α-ethyl chenodeoxycholic acid;(6-ECDCA), INT-747;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) - fed and fasted | maximum concentration (observed) | Day 1 and Day 14: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 14 hours | 
| Time to maximum concentration (Tmax) | Time to maximum concentration | 24 hours | 
| Area under the concentration versus time (AUCt) | Area under the concentration versus time curve from time 0 to the last sampling time with measurable analyte concentration. | 216 hours | 
| Area under the concentration versus time curve from 0 to 24 hours (AUC 0-24) | Area under the concentration versus time curve from 0 to 24 hours with measurable analyte concentration | 24 hours |