A Drug-Drug Interaction Study Between Fenofibric Acid and Efavirenz

An Open-label, Drug Interaction Study to Investigate the Effects of Steady-State Fenofibric Acid on the Single-Dose Pharmacokinetics of Efavirenz in Healthy Subjects

Efavirenz is predominantly metabolized by cytochrome P450 (CYP) 2B6. Fenofibric Acid is an inhibitor of CYP2B6. This study will evaluate the effect of multiple doses of fenofibric acid at steady-state on the pharmacokinetics of single-dose efavirenz in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: efavirenz; Drug: fenofibric acid 105 mg

Detailed Description

Efavirenz is predominantly metabolized by cytochrome P450 (CYP) 2B6. Fenofibric Acid is an inhibitor of CYP2B6. This study will evaluate the effect of multiple doses of fenofibric acid at steady-state on the pharmacokinetics of single-dose efavirenz in healthy adult subjects. This study will not evaluate the the effects of efavirenz on fenofibric acid pharmacokinetics. On study Day 1 after a fast of at least 10 hours, thirty healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one oral dose of efavirenz (1 x 600 mg tablet). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of efavirenz. Blood sampling will then continue on a non-confined basis at 48, 72, 96 and 120 hours post-dose. A 21 day washout period will be completed after the first dose of efavirenz on Day 1. On Days 22 through 30, all subjects will receive a single oral dose of fenofibric acid (1 x 105 mg tablet) in the morning without regard to meals. On the morning of Day 31 after a fast of at least 10 hours, all study participants will receive co-administered single oral doses of efavirenz (1 x 600 mg tablet) and fenofibric acid (1 x 105 mg tablet). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately determine the pharmacokinetics of efavirenz. Blood sampling will then continue on a non-confined basis at 48, 72, 96 and 120 hours post-dose. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Vital signs (seated blood pressure and pulse) will be measured prior to dosing and at approximately 1, 2, 3 and 5 hours post-dose on Days 1, 22 and 31 to coincide with peak plasma concentrations of both efavirenz and fenofibric acid. Blood pressure and pulse will also be obtained at 24 hours post-dose on Days 2 and 32 prior to discharge from the clinical study unit. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the Investigator and reported in the subject's case report form.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • INC Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adults 18-45 years of age, non-smoking and non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures), with a body mass index (BMI) greater or equal to 18 and less than or equal to 32kg/m2, hemoglobin >12 g/dL.

Exclusion Criteria:

• recent participation (within past month) 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, psychiatric disease or active sexually transmitted 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 or sensitivities to efavirenz, fenofibrate, fenofibric acid or any component of the two formulations
• Subjects who have had a tattoo or body piercing within 30 days prior to administration of study medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Efavirenz 600mg alone; efavirenz 600mg by mouth taken on Day 1	Drug: efavirenz; 600 mg; Other Names: SUSTIVA
Active Comparator: Efavirenz co-administered with fenofibric acid; co-administered oral doses of efavirenz 600 mg and fenofibric acid 105 mg taken on Day 31	Drug: efavirenz; 600 mg; Other Names: SUSTIVA; Drug: fenofibric acid 105 mg; fenofibric acid 105 mg; Other Names: FIBRICOR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Maximum Plasma Concentration (Cmax)	The maximum or peak concentration that the drug reaches in the plasma for efavirenz	serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 31 and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, 96, and 120 hours after dose administration
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time 0 to Time t[AUC(0-t)]	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 for efavirenz	serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 31 and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, 96, and 120 hours after dose administration
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-infinity]	The area under the plasma concentration versus time curve from time 0 to infinity. [AUC(0 to infinity)] was calculated as the sum of AUC (0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant for efavirenz.	serial pharmacokinetic blood samples drawn immediately prior to dosing on Days 1 and 31 and then 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, 96, and 120 hours after dose administration

Collaborators and Investigators

• Sponsor: Mutual Pharmaceutical Company, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: November 11, 2011
• First Submitted That Met QC Criteria: November 11, 2011
• First Posted (Estimate): November 16, 2011

Study Record Updates

• Last Update Posted (Estimate): August 1, 2012
• Last Update Submitted That Met QC Criteria: July 30, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fenofibric acid; Efavirenz
• Other Study ID Numbers: MPC-028-11-1001