Drug-Drug Interaction Study Between Fenofibric Acid and Efavirenz

• Maximum Plasma Concentration (Cmax) of Efavirenz [ Time Frame: 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. ] [ Designated as safety issue: No ]
  The maximum or peak concentration that efavirenz reaches in the plasma.
  
  
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] [ Time Frame: 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 ] [ Designated as safety issue: No ]
  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.
  
  
• Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [ Time Frame: 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 ] [ Designated as safety issue: No ]
  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.
  
  

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.