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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: OCA 5 mg; Drug: OCA 10 mg; Drug: OCA 25 mg

• Registration Number: NCT01933503
• Lead Sponsor: Intercept Pharmaceuticals

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).

Detailed Description

Twenty-four eligible subjects will be enrolled and randomized to 1 of 3 treatment groups (5 mg, 10 mg, or 25 mg) in a treatment ratio of 1:1:1 and no less than a ratio of 1:1 for female: male subjects. The study comprises single dose and multiple dose phases. The randomized dose administered in the single dose phase will be the subject's dose level for the multiple dose phase. A single dose of OCA (5 mg, 10 mg, or 25 mg) will be administered on Day 1. PK, safety, and tolerability will then be assessed for 3 days. On Day 4, the multiple dose phase will begin at the same dose level (5 mg, 10 mg, or 25 mg), with subjects receiving OCA once daily for 14 days. PK, safety, and tolerability will be assessed for 2 weeks at the clinical site following the last investigational product (IP) dose on Day 17. Subjects will be confined at the inpatient trial site from Day 0 until the morning of Day 30. They will return to the study site on Day 37 for follow up.

Study Timeline

• Study First Submitted: 2013-08-28
• Study First Submitted QC: 2013-08-28
• Study First Posted: 2013-09-02
• Study Start: 2013-10
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-04
• Last Update Posted: 2013-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded from the trial:

1. Prior exposure to OCA (INT-747; 6-ECDCA)
2. History of known or suspected clinically significant hypersensitivity to OCA or any of its components
3. 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)
4. History of gastrointestinal surgeries or gall bladder removal (cholecystectomy)
5. History or presence of a clinically significant cardiovascular, hepatic, diabetic, gastrointestinal, metabolic, neurologic, pulmonary, endocrine, psychiatric, or neoplastic disorder(s)
6. History of known or suspected clinically significant hypersensitivity to any drug, aside from penicillin
7. 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
8. 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
9. 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
10. History or presence of substance abuse within the past 2 years or positive drug screen tests
11. Smoker or use of any tobacco or nicotine containing products
12. Any screening laboratory test for which the results are not within the normal reference range and considered clinically significant
13. Participation in another investigational drug trial within 30 days prior to Day 0
14. History of noncompliance to medical regimens, or subjects who are considered to be potentially unreliable
15. Blood or plasma donation within 30 days prior to Day 0
16. Mental instability or incompetence
17. Presence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) at screening
18. Known or suspected Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OCA 5 mg	OCA 5 mg	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.
OCA 10 mg	OCA 10 mg	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.
OCA 25 mg	OCA 25 mg	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.

Primary Outcome Measures

Name	Time	Method
Area under the concentration vs. time curve (AUCt)	3 days - single dose, 33 days - Multi dose	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
Area under the concentration vs. time curve from time 0 to 24 hours (AUC0-24)	24 hours	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
The ratio of each conjugate to OCA	3 days - single dose, 33 days - Multi dose	The ratio of each conjugate to OCA for exposure PK parameters for both single and multiple dose assessments.
Accumulation ratios (Rac) based on AUC, Cmax and Cmin	17 days	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
Maximum concentration (Cmax observed)	3 days - single dose, 33 days - Multi dose	Maximum concentration (observed) following single and multiple doses of OCA 5 mg, 10 mg, and 25 mg
Time to maximum concentration (tmax)	3 days - single dose, 33 days - Multi dose	Time to maximum concentration (tmax)

Trial Locations

Locations (1)

Spaulding Clinical Research; 🇺🇸 West Bend, Wisconsin, United States