Single Dose and Multiple Dose Trial to Assess Pharmacokinetics of Obeticholic Acid (OCA)

NCT01933503 | Completed Phase 1 DMC

• 1 other identifier: 747-105
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open label, randomized, parallel design, single and multiple dose trial to evaluate the pharmacokinetics(PK), safety and tolerability of obeticholic acid (OCA).

Conditions

Healthy

Keywords

MAD; SAD; Obeticholic Acid (OCA)

Outcome Measures

Primary Outcomes (6)

• Maximum concentration (Cmax observed)

  Maximum concentration (observed) following single and multiple doses of OCA 5 mg, 10 mg, and 25 mg

  3 days - single dose, 33 days - Multi dose

• Time to maximum concentration (tmax)

  Time to maximum concentration (tmax)

  3 days - single dose, 33 days - Multi dose

• Area under the concentration vs. time curve (AUCt)

  Area under the concentration vs. time curve (AUCt) from time 0 to the last sampling time with measurable analyte concentration, calculated by the linear trapezoidal method

  3 days - single dose, 33 days - Multi dose

• Area under the concentration vs. time curve from time 0 to 24 hours (AUC0-24)

  Area under the concentration vs. time curve from time 0 to 24 hours (AUC0-24) with measurable analyte concentration, calculated by the linear trapezoidal method

  24 hours

• The ratio of each conjugate to OCA

  The ratio of each conjugate to OCA for exposure PK parameters for both single and multiple dose assessments.

  3 days - single dose, 33 days - Multi dose

• Accumulation ratios (Rac) based on AUC, Cmax and Cmin

  Accumulation ratios (Rac) based on AUC, Cmax and Cmin will be calculated for OCA and its conjugates (glyco-OCA and tauro-OCA) from Day 1 to Day 17

  17 days

Study Arms (3)

OCA 5 mg

EXPERIMENTAL

OCA 5 mg, 1 mg by mouth followed by 2 days of no investigational product (IP); then OCA 5 mg by mouth for 14 days.

Drug: OCA 5 mg

OCA 10 mg

EXPERIMENTAL

OCA 10 mg, 1 mg by mouth followed by 2 days of no investigational product (IP); then OCA 10 mg by mouth for 14 days.

Drug: OCA 10 mg

OCA 25 mg

EXPERIMENTAL

OCA 25 mg, 1 mg by mouth followed by 2 days of no investigational product (IP); then OCA 25 mg by mouth for 14 days.

Drug: OCA 25 mg

Interventions

OCA 5 mg DRUG

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

OCA 5 mg

OCA 10 mg DRUG

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

OCA 10 mg

OCA 25 mg DRUG

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

OCA 25 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the trial:
• Prior exposure to OCA (INT-747; 6-ECDCA)
• History of known or suspected clinically significant hypersensitivity to OCA or any of its components
• 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 (IBD)
• 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, including oral contraceptives and bile acid sequestrants, within 14 days prior to IP dosing or ingestion of an over the counter medication within 7 days prior to IP dosing
• 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) or positive alcohol tests
• History or presence of substance abuse within the past 2 years or positive drug screen tests
• Smoker or use of any tobacco or nicotine containing 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

Sponsors & Collaborators

• Intercept Pharmaceuticals: lead

Study Sites (1)

Spaulding Clinical Research

West Bend, Wisconsin, 53095, United States

Location

Related Publications (2)

• Friedman ES, Li Y, Shen TD, Jiang J, Chau L, Adorini L, Babakhani F, Edwards J, Shapiro D, Zhao C, Carr RM, Bittinger K, Li H, Wu GD. FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid. Gastroenterology. 2018 Dec;155(6):1741-1752.e5. doi: 10.1053/j.gastro.2018.08.022. Epub 2018 Aug 23.

  PMID: 30144429 DERIVED

• 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 Shaprio, M.D.

  Intercept Pharmaceuticals, San Diego, CA 92122

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 28, 2013
• First Posted: September 2, 2013
• Study Start: October 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: December 5, 2013

Record last verified: 2013-12

Locations

US (1)