Drug-Drug Interaction Study Between Fenofibric Acid and Efavirenz

Study Overview
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Brief Summary
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Efavirenz is predominantly metabolized by cytochrome P450 (CYP) 2B6. Fenofibric Acid is an inhibitor of CYP 2B6. 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.

Detailed Description
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Efavirenz is predominantly metabolized by cytochrome P450 (CYP) 2B6. Fenofibric Acid is an inhibitor of CYP 2B6. 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. 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 120 hours post-dose at times sufficient to adequately define the pharmacokinetics of efavirenz. 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 120 hours post-dose at times sufficient to adequately determine the pharmacokinetics of efavirenz. 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 and 31 and prior to dosing and at approximately 1, 2 and 4 hours post-dose on Day 22 to coincide with peak plasma concentrations of both efavirenz and fenofibric acid. 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.

Official Title
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An Open-Label Drug Interaction Study to Investigate the Effects of Steady State Fenofibric Acid on the Single-Dose Pharmacokinetics of Efavirenz in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Efavirenz 600 mg
* Drug: Efavirenz 600 mg
* Drug: Fenofibric Acid


Participation Criteria
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Eligibility Criteria
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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 fenofibric acid or efavirenz

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Efavirenz Alone<br>Baseline Efavirenz pharmacokinetics. | Drug: Efavirenz 600 mg<br>* Efavirenz 600 mg administered as a single oral dose on the morning of Day 1.<br>|
| Experimental: Efavirenz with Steady State Fenofibric Acid<br>Efavirenz pharmacokinetics in the presence of steady state Fenofibric Acid. | Drug: Efavirenz 600 mg<br>* Co-administered single oral doses of Efavirenz 600 mg and Fenofibric Acid 105 mg on Day 31.<br>Drug: Fenofibric Acid<br>* Co-administered single oral doses of Efavirenz 600 mg and Fenofibric Acid 105 mg on Day 31.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of Efavirenz | The maximum or peak concentration that efavirenz reaches in the plasma. | serial pharmacokinetic blood samples drawn 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. | 
| 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 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 | 
| Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy, adult, efavirenz, fenofibric acid, blood levels