Healthy
Conditions
Keywords
pharmacokinetics
Brief summary
The primary objective of this study is to characterize the single-dose pharmacokinetic profile of fenofibric acid (105 mg tablets) and the effect of food of various calorie/fat compositions on the rate and extent of absorption. Additionally, the safety and tolerability of this dose and regimen of fenofibric acid will be evaluated.
Detailed description
The primary objective of this study is to determine the single-dose pharmacokinetic profile of fenofibric acid (105 mg tablets) and the effect of food of various calorie/fat compositions on the rate and extent of absorption. Forty healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 years old will receive a single oral dose of fenofibric acid in one of four randomly assigned sequences of meal conditions each separated by a 7 day washout period. On study Days 1, 8, 15 and 22 each subject will receive a single oral dose (1 x 105 mg tablet) of fenofibric acid following an overnight fast of at least 10 hours or with a low-fat meal, standard meal, or high-fat/high-calorie meal according to their randomization sequence. Subjects will fast for at least 4.25 hours after dosing in each of the four dosing conditions. Blood samples will be drawn from all participants before dosing and for 72 hours post-dose at times sufficient to adequately define the pharmacokinetics of fenofibric acid. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Seated blood pressure and heart rate will be measured prior to dosing and at 2 hours post-dose. Subjects will be monitored throughout the confinement portion of the study for adverse reactions to the study drug and/or procedures. 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.
Interventions
One 105 mg tablet administered 30 minutes after the initiation of a low-fat breakfast.
Sponsors
Mutual Pharmaceutical Company, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults between the ages of 18 and 45 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Non-obese, non-smoking, healthy adult volunteers consisting of members of the community-at-large were enrolled.
Pre-assignment details
88 subjects were screened and 51 were screen failures. Enrollment of 40 subjects was planned, however, the enrollment of 37 subjects was judged to be sufficient to meet the criterion of 36 necessary to complete the study.
Participants by arm
| Arm | Count |
|---|---|
| Low-Fat Meal, Standard Meal, High Fat/High Calorie Meal,Fasted All subjects received each of the four study regimens in a randomly assigned sequence of dosing periods. On the mornings of Days 1, 8, 15 and 22 each subject received one tablet of fenofibric acid 105 mg administered after one of the following meal conditions: 1) low-fat meal, 2) standard meal, 3) high-fat/high-calorie meal 4) overnight fast of at least 10 hours. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Washout Period of 7 Days | Adverse Event | 0 | 0 | 1 | 0 |
| Washout Period of 7 Days | Withdrawal by Subject | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Low-Fat Meal, Standard Meal, High Fat/High Calorie Meal,Fasted |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Age Continuous | 23.89 years STANDARD_DEVIATION 6.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 35 | 2 / 36 | 4 / 35 | 4 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 36 | 0 / 35 | 0 / 35 |
Outcome results
Primary
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.
Time frame: 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
Population: Pharmacokinetic analyses of fenofibric acid are based on 34 subjects who completed the study. One subject discontinued due to an adverse event and two subjects discontinued for personal reasons.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-fat Meal - Treatment A | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 132,636.84 ng-hr/mL |
| Standard Meal - Treatment B | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 134,928.11 ng-hr/mL |
| High-Fat, High-Calorie Meal - Treatment C | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 134,814.42 ng-hr/mL |
| Fasted - Treatment D | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 139,975.28 ng-hr/mL |
Primary
Maximum Plasma Concentration (Cmax)
The maximum or peak concentration that the drug reaches in the plasma.
Time frame: 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
Population: Pharmacokinetic analyses of fenofibric acid are based on 34 subjects who completed the study. One subject discontinued due to an adverse event and two subjects discontinued for personal reasons.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-fat Meal - Treatment A | Maximum Plasma Concentration (Cmax) | 9,806.74 ng/mL |
| Standard Meal - Treatment B | Maximum Plasma Concentration (Cmax) | 9,854.39 ng/mL |
| High-Fat, High-Calorie Meal - Treatment C | Maximum Plasma Concentration (Cmax) | 7,950.75 ng/mL |
| Fasted - Treatment D | Maximum Plasma Concentration (Cmax) | 12,061.67 ng/mL |
Primary
The Area Under the Plasma Concentration Versus Time Curve From Time 0 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.
Time frame: 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.
Population: Pharmacokinetic analyses of fenofibric acid are based on 34 subjects who completed the study. One subject discontinued due to an adverse event and two subjects discontinued for personal reasons.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low-fat Meal - Treatment A | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 145,827.10 ng-hr/mL |
| Standard Meal - Treatment B | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 148,367.21 ng-hr/mL |
| High-Fat, High-Calorie Meal - Treatment C | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 148,488.53 ng-hr/mL |
| Fasted - Treatment D | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 152,571.61 ng-hr/mL |