A Drug-Drug Interaction Study Between Fenofibric Acid and Efavirenz

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: efavirenz
Drug: fenofibric acid 105 mg

Registration Number: NCT01472380

Lead Sponsor: Mutual Pharmaceutical Company, Inc.

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Efavirenz co-administered with fenofibric acid	efavirenz	co-administered oral doses of efavirenz 600 mg and fenofibric acid 105 mg taken on Day 31
Efavirenz co-administered with fenofibric acid	fenofibric acid 105 mg	co-administered oral doses of efavirenz 600 mg and fenofibric acid 105 mg taken on Day 31
Efavirenz 600mg alone	efavirenz	efavirenz 600mg by mouth taken on Day 1

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Maximum Plasma Concentration (Cmax)	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	The maximum or peak concentration that the drug reaches in the plasma for efavirenz
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time 0 to Time t[AUC(0-t)]	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	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
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-infinity]	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	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.