Healthy
Conditions
Keywords
healthy, pharmacokinetics, therapeutic equivalency, fenofibric acid
Brief summary
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. Safety and tolerability of these regimens will also be evaluated.
Detailed description
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.
Interventions
DRUGFenofibric Acid 35 mg Tablet
1 x 35 mg tablet administered after an overnight fast of at least 10 hours
105 mg tablet administered after an overnight fast of at least 10 hours
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 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. 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. |
Participant flow
Recruitment details
Fifty-Four (54) non-obese, non-smoking, healthy adult volunteers from the community at large were enrolled.
Pre-assignment details
One hundred and eight (108) subjects were screened. Thirty-six (36) subjects were screen failures. Of the remaining seventy-two (72) subjects, fifty-six (56) checked in and fifty-four (54) were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Fenofibric Acid - Treatments A, B and C All subjects received each of the three study regimens in a randomly assigned sequence of dosing periods. On the mornings of Days 1, 8 and 15 each subject received either one 35 mg fenofibric acid tablet (treatment A), three 35 mg fenofibric acid tablets (105 mg total dose, treatment B) or one 105 mg fenofibric acid tablet (treatment C). | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Washout Period of 7 Days | due to concomitant medication used | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Fenofibric Acid - Treatments A, B and C |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants |
| Age Continuous | 24.46 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 46 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 53 | 4 / 54 | 5 / 53 |
| serious Total, serious adverse events | 0 / 53 | 0 / 54 | 0 / 53 |
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. 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.
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 53 out of the 54 subjects who completed the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fenofibric Acid 35 mg (1 x 35 mg Tablet) - Treatment A | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 49,419.89 ng-hr/mL |
| Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg) | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 148,259.66 ng-hr/mL |
| Fenofibric Acid 105 mg (3 x 35 mg Tablet) - Treatment B | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 131,976.95 ng-hr/mL |
| Fenofibric Acid 105 mg (1 x 105 mg Tablet) - Treatment C | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 135,119.10 ng-hr/mL |
Primary
Maximum Plasma Concentration (Cmax)
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.
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 53 out of the 54 subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fenofibric Acid 35 mg (1 x 35 mg Tablet) - Treatment A | Maximum Plasma Concentration (Cmax) | 3,569.47 ng/mL | Standard Deviation 685.12 |
| Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg) | Maximum Plasma Concentration (Cmax) | 10,708.40 ng/mL | — |
| Fenofibric Acid 105 mg (3 x 35 mg Tablet) - Treatment B | Maximum Plasma Concentration (Cmax) | 11,014.93 ng/mL | — |
| Fenofibric Acid 105 mg (1 x 105 mg Tablet) - Treatment C | Maximum Plasma Concentration (Cmax) | 11,202.87 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. 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.
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 53 out of the 54 subjects who completed the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fenofibric Acid 35 mg (1 x 35 mg Tablet) - Treatment A | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 58,304.35 ng-hr/mL |
| Fenofibric Acid 35 mg (35 mg Dose-adjusted to 105 mg) | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 174,913.04 ng-hr/mL |
| Fenofibric Acid 105 mg (3 x 35 mg Tablet) - Treatment B | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 142,858.88 ng-hr/mL |
| Fenofibric Acid 105 mg (1 x 105 mg Tablet) - Treatment C | The Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity AUC(0-∞) | 147,555.58 ng-hr/mL |