Fed Bioequivalence Study of Fenofibric Acid Versus TriCor® (Fenofibrate)

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Fenofibrate (Tricor®) 145 mg Tablet; Drug: Fenofibric Acid (Fibricor™) 105 mg Tablet

• Registration Number: NCT00960687
• Lead Sponsor: Mutual Pharmaceutical Company, Inc.

Brief Summary

This study will evaluate the bioequivalence of 105 mg fenofibric acid tablets relative to 145 mg fenofibrate tablets in healthy volunteers when administered following a breakfast of standard composition. Safety and tolerability of this regimen will also be evaluated.

Detailed Description

Fenofibrate is rapidly and completely hydrolyzed to fenofibric acid, the active moiety. The primary objective of this study is to evaluate the bioequivalence of 105 mg fenofibric acid tablets relative to 145 mg fenofibrate tablets in healthy volunteers when administered following a breakfast of standard composition. Additionally, the safety and tolerability of this dosing regimen will be evaluated. Fifty-four healthy, non-smoking, non-obese, 18-45 year old, male and female volunteers will be randomly assigned in a crossover fashion to receive each of two dosing regimens (fenofibric acid and fenofibrate) in sequence with a 7 day washout period between dosing periods. On the morning of Day 1, subjects will receive either a single oral dose of the test formulation, fenofibric acid (1 x 105 mg tablet) or a single oral dose of the reference formulation, fenofibrate (1 x 145 mg tablet) 30 minutes after the initiation of a standard breakfast. After a 7 day washout period, on the morning of Day 8, subjects will receive the alternate regimen 30 minutes after the initiation of a standard breakfast. Fasting will continue for 4 hours after each dose. Blood samples will be drawn from all participants before dosing and for 72 hours post dose at times sufficient to adequately define the pharmacokinetics of fenofibric acid. Subjects will be monitored throughout their participation for adverse reactions to the study drug and/or procedures. Seated blood pressure and pulse will be measured prior to each dose and approximately 2 hours post-dose. All adverse experiences, whether elicited by query, spontaneously reported, or observed by clinic staff, will be documented in the subject's case report form.

Study Timeline

• Study Start: 2007-10
• Primary Completion: 2007-11
• Study Completion: 2007-11
• Study First Submitted: 2009-08-14
• Study First Submitted QC: 2009-08-17
• Study First Posted: 2009-08-18
• Results First Submitted: 2009-08-27
• Status Verified: 2009-10
• Results First Submitted QC: 2009-10-08
• Results First Posted: 2009-10-14
• Last Update Submitted: 2009-10-16
• Last Update Posted: 2009-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• Healthy adults 18-45 years of age
• Non-smoking
• Non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures)
• Body mass index (BMI) less than 30
• Medically healthy on the basis of medical history and physical examination
• Hemoglobin > or = to 12g/dL
• Completion of the screening process within 28 days prior to dosing
• Provision of voluntary written informed consent

Exclusion Criteria

• Recent participation (within 28 days) in other research studies
• Recent significant blood donation or plasma donation
• Pregnant or lactating
• Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)
• Recent (2-year) history or evidence of alcoholism or drug abuse
• History or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 28 days prior to the first dose and throughout the study
• Drug allergies to fenofibrate (fenofibric acid)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Fenofibrate (Tricor®)	Fenofibrate (Tricor®) 145 mg Tablet	1 x 145 mg fenofibrate (Tricor®) tablet administered 30 minutes after the initiation of a standard breakfast.
Fenofibric Acid (Fibricor™)	Fenofibric Acid (Fibricor™) 105 mg Tablet	1 x 105 mg fenofibric acid (Fibricor™)tablet administered 30 minutes after the initiation of a standard breakfast.

Primary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax)	serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after drug administration.	The maximum or peak concentration that the drug reaches in the plasma.
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]	serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after drug administration.	The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule.
The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞)	serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after drug administration.	The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant.