Healthy
Conditions
Keywords
healthy, pharmacokinetics, therapeutic equivalency
Brief summary
This study will evaluate the bioequivalence of 105 mg fenofibric acid tablets relative to 145 mg fenofibrate tablets in healthy volunteers when administered following a breakfast of standard composition. Safety and tolerability of this regimen will also be evaluated.
Detailed description
Fenofibrate is rapidly and completely hydrolyzed to fenofibric acid, the active moiety. The primary objective of this study is to evaluate the bioequivalence of 105 mg fenofibric acid tablets relative to 145 mg fenofibrate tablets in healthy volunteers when administered following a breakfast of standard composition. Additionally, the safety and tolerability of this dosing regimen will be evaluated. 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 two dosing regimens (fenofibric acid and fenofibrate) in sequence with a 7 day washout period between dosing periods. On the morning of Day 1, subjects will receive either a single oral dose of the test formulation, fenofibric acid (1 x 105 mg tablet) or a single oral dose of the reference formulation, fenofibrate (1 x 145 mg tablet) 30 minutes after the initiation of a standard breakfast. After a 7 day washout period, on the morning of Day 8, subjects will receive the alternate regimen 30 minutes after the initiation of a standard breakfast. Fasting will continue for 4 hours after each dose. 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. 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 post-dose. All adverse experiences, whether elicited by query, spontaneously reported, or observed by clinic staff, will be documented in the subject's case report form.
Interventions
1 x 105 mg fenofibric acid (Fibricor™) tablet administered 30 minutes after the initiation of a standard breakfast.
1 x 145 mg Fenofibrate (Tricor®) tablet administered 30 minutes after the start of a standard 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 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 fenofibrate (fenofibric acid)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | 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 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 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 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. |
Participant flow
Recruitment details
Fifty-Four (54) non-obese, non-smoking, healthy adult volunteers, consisting of members of the community-at-large, were enrolled.
Pre-assignment details
Ninety-nine (99) subjects were screened. Forty-five (45) subjects were screen failures. The remaining fifty-four subjects were enrolled, 47 of whom completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Fenofibric Acid 105 mg Tablets and Fenofibrate 145 mg Tablets All subjects received each of the two study regimens in a randomly assigned sequence of dosing periods. On the mornings of Day 1 and Day 8, each subject received one tablet of either fenofibric acid 105 mg or fenofibrate 145 mg, 30 minutes after the initiation of a standard meal. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period of 7 Days | Adverse Event | 3 | 2 |
| Washout Period of 7 Days | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Fenofibric Acid 105 mg Tablets and Fenofibrate 145 mg Tablets |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants |
| Age Continuous | 24.4 years STANDARD_DEVIATION 6.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 51 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 51 | 5 / 50 |
| serious Total, serious adverse events | 0 / 51 | 0 / 50 |
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 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 are based on 47 out of 54 enrolled subjects who completed this study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fenofibric Acid 105 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 121,974.07 ng-hr/mL |
| Fenofibrate 145 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 132,463.37 ng-hr/mL |
Primary
Maximum Plasma Concentration (Cmax)
The maximum or peak concentration that the drug reaches in the plasma.
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 are based on 47 out of 54 enrolled subjects who completed this study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fenofibric Acid 105 mg Tablets | Maximum Plasma Concentration (Cmax) | 8,545.50 ng/mL |
| Fenofibrate 145 mg Tablets | Maximum Plasma Concentration (Cmax) | 9,456.66 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 are based on 47 out of 54 enrolled subjects who completed this study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fenofibric Acid 105 mg Tablets | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 134,576.33 ng-hr/mL |
| Fenofibrate 145 mg Tablets | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 146,847.53 ng-hr/mL |