Fasted Pharmacokinetic and Bioequivalency Study of Fenofibric Acid

This study will evaluate the pharmacokinetic linearity of a single 35 mg fenofibric acid dose and demonstrate the bioequivalence of three 35 mg fenofibric acid tablets (105 mg total single dose) to a single 105 mg fenofibric acid tablet in healthy adult volunteers when each dose is administered under fasted conditions. 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 three fenofibric acid dosing regimens in sequence with a 7 day washout period between dosing periods. On the morning of the first day of each dosing period, after an overnight fast of at least 10 hours, subjects will receive single doses of fenofibric acid (1 x 35 mg tablet), fenofibric acid (3 x 35 mg tablets - 105 mg total dose), or fenofibric acid (1 x 105 mg tablet). Fasting will continue for 4 hours after dose administration. Blood samples will be drawn from all participants prior to dosing and for 72 hours post-dose, at times sufficient to adequately define fenofibric acid pharmacokinetics. 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 after each dose to coincide with peak plasma concentrations. All adverse experiences, whether elicited by query, spontaneously reported, or observed by clinic staff, will be documented in the subject's case report form.

• Fenofibric Acid 35 mg Tablet (Drug): 1 x 35 mg tablet administered after an overnight fast of at least 10 hours
• Fenofibric Acid 35 mg Tablet (Drug): 3 x 35 mg tablets administered after an overnight fast of at least 10 hours
• Fenofibric Acid 105 mg Tablet (Drug): 105 mg tablet administered after an overnight fast of at least 10 hours

Primary outcomes

• Maximum Plasma Concentration (Cmax) [serial pharmacokinetic blood samples drawn immediately prior to dosing and then 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 dose administration]: The maximum or peak concentration that the drug reaches in the plasma. For the dosing group, Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg), the Cmax values were dose-adjusted in order to assess pharmacokinetic linearity.
• 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 and then 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 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 the dosing group, Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg), the \[AUC(0-t)\] values were dose-adjusted in order to assess pharmacokinetic linearity.
• 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. For the dosing group, Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg), the AUC(0-∞) values were dose-adjusted in order to assess pharmacokinetic linearity.

Sex: All, ages: 18 Years to 45 Years, accepts healthy volunteers

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

Participant flow

Outcome results

• Maximum Plasma Concentration (Cmax) (Primary), Mean, ng/mL: Fenofibric Acid 35 mg (1 x 35 mg Tablet) - Treatment A 3,569.47 +/- 685.12; Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg) 10,708.40 +/- 2,055.36; Fenofibric Acid 105 mg (3 x 35 mg Tablet) - Treatment B 11,014.93 +/- 2,033.94; Fenofibric Acid 105 mg (1 x 105 mg Tablet) - Treatment C 11,202.87 +/- 2,470.61
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] (Primary), Mean, ng-hr/mL: Fenofibric Acid 35 mg (1 x 35 mg Tablet) - Treatment A 49,419.89 +/- 18,188.17; Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg) 148,259.66 +/- 54,564.52; Fenofibric Acid 105 mg (3 x 35 mg Tablet) - Treatment B 131,976.95 +/- 41,086.74; Fenofibric Acid 105 mg (1 x 105 mg Tablet) - Treatment C 135,119.10 +/- 42,326.25
• The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) (Primary), Mean, ng-hr/mL: Fenofibric Acid 35 mg (1 x 35 mg Tablet) - Treatment A 58,304.35 +/- 20,877.56; Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg) 174,913.04 +/- 62,632.68; Fenofibric Acid 105 mg (3 x 35 mg Tablet) - Treatment B 142,858.88 +/- 45,554.44; Fenofibric Acid 105 mg (1 x 105 mg Tablet) - Treatment C 147,555.58 +/- 48,994.99

Adverse events

Other adverse events by term

• Anthony R Godfrey, Pharm.D., Principal investigator, PRACS Institute