Healthy
Conditions
Keywords
Therapeutic Equivalency
Brief summary
The purpose of this study is to evaluate and compare the relative bioavailability and therefore the bioequivalence of a test formulation of Lovastatin tablets to an equivalent dose of Mevacor® tablets after a single oral dose administered under fed conditions.
Detailed description
The purpose of this study is to evaluate and compare the relative bioavailability and therefore the bioequivalence of a test formulation of Lovastatin tablets to an equivalent dose of Mevacor® tablets after a single oral dose administered under fed conditions. Fifty-four healthy, light/non/or ex-smoking, non-obese, male volunteers at least 18 years of age will be randomly assigned in a crossover fashion to receive each of two Lovastatin dosing regimens in sequence with a 7 day washout period between dosing periods. On the morning of Day 1, after an overnight fast of at least 10 hours, subjects will receive a standardized high-fat, high-calorie meal 30 minutes before drug administration. Thirty minutes after the start of the breakfast, a single oral dose of either the test formulation, Lovastatin (1 x 40 mg tablet), or a single oral dose of the reference formulation, Mevacor® (1 x 40 mg tablet) will be administered. After a 7 day washout period, on the morning of Day 8, following an overnight fast of at least 10 hours and 30 minutes after the start of a standardized high-fat, high-calorie meal, subjects will receive the alternate regimen. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of Lovastatin. Blood sampling will then continue on a non-confined basis at 36 and 48 hours post-dose. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout the confinement portion of the study for adverse reactions to the study drug and/or procedures. Vital signs will be monitored if judged necessary by the physician in charge. 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
40 mg tablet administered 30 minutes following the start of a standardized high-fat, high-calorie breakfast
40 mg tablet administered 30 minutes following the start of a standardized high-fat, high-calorie breakfast
Sponsors
Mutual Pharmaceutical Company, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Availability of volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by the informed consent form (ICF) duly signed by the volunteer * Male aged of at least 18 with a body mass index (BMI) greater than or equal to 19 and below 30 kg/m² * Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance * Healthy according to the laboratory results and physical examination * Light-, non- or ex-smokers. Light smokers are defined as someone smoking 10 cigarettes or less per day, and ex-smokers are defined as someone who completely stopped smoking for at least 3 months * The informed consent must be signed by all volunteers, prior to their participation in the study
Exclusion criteria
* Significant history of hypersensitivity to lovastatin or any related products as well as severe hypersensitivity reactions (like angioedema) to any drugs * Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects * History of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability, including but not limited to cholecystectomy * Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease * Presence of active liver disease or unexplained persistent elevations of serum transaminases * Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (\>3 units of alcohol per day, intake of excessive alcohol, acute or chronic) * Any clinically significant illness in the previous 28 days before day 1 of this study * Use of enzyme-modifying drugs in the previous 28 days before day 1 of this study (all barbiturates, corticosteroids, phenylhydantoins, etc.) * Participation in another clinical trial in the previous 28 days before day 1 of this study * Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study * Positive urine screening of drugs of abuse * Positive results to HIV, HBsAg or anti-HCV tests
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 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 14, 18, 24, 36, and 48 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 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 14, 18, 24, 36, and 48 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. |
| Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 14, 18, 24, 36, and 48 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
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lovastatin 40 mg Tablets and Mevacor® 40 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 Lovastatin 40 mg or Mevacor® 40 mg thirty minutes after the start of a standardized high-fat, high-calorie breakfast. | 54 |
| Total | 54 |
Baseline characteristics
| Characteristic | Lovastatin 40 mg Tablets and Mevacor® 40 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 | 42 years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 52 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 54 | 20 / 54 |
| serious Total, serious adverse events | 0 / 54 | 0 / 54 |
Outcome results
Primary
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated 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 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 14, 18, 24, 36, and 48 hours after drug administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lovastatin 40 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | 48.72 ng-hr/mL | Standard Deviation 29.14 |
| Mevacor® 40 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | 52.98 ng-hr/mL | Standard Deviation 34.38 |
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 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 14, 18, 24, 36, and 48 hours after drug administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lovastatin 40 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 47.86 ng-hr/mL | Standard Deviation 29.34 |
| Mevacor® 40 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 51.64 ng-hr/mL | Standard Deviation 33.05 |
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 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 14, 18, 24, 36, and 48 hours after drug administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lovastatin 40 mg Tablets | Maximum Plasma Concentration (Cmax) | 9.26 ng/mL | Standard Deviation 6.13 |
| Mevacor® 40 mg Tablets | Maximum Plasma Concentration (Cmax) | 10.01 ng/mL | Standard Deviation 7.06 |