Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the rate and extent of absorption of a test formulation of Levetiracetam tablets versus the reference Keppra® administered as a 1 x 750 mg tablet under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGLevetiracetam
750 mg Tablet
DRUGKeppra®
750 mg Tablet
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or Female, smoker or non-smoker, between the ages of 18 years and 55 years. * BMI greater than or equal to 19.0 and less than 30.0 kg/m2.
Exclusion criteria
Subjects to whom any of the following applies will be excluded from the study: * Clinically significant illnesses or surgery within 4 weeks of the administration of study medication. * Any clinically significant abnormality or abnormal laboratory test results found during medical screening. * Any reason which, in the opinion of the medical subinvestigator, would prevent the subject from participating in the study. * Positive testing for hepatitis B, hepatitis C or HIV at screening. * ECG abnormalities (clinically significant) or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, or diastolic blood pressure lower than 50 or over 90; or heart rate less than 50 bpm or over 100 bpm) at screening. * History of significant alcohol abuse or drug abuse within one year prior to the screening visit. * Regular use of alcohol within six months prior to the screening visit (more than fourteen units of alcohol per week \[1 Unit = 150 mL of wine, 360 mL of beer or 45 mL of 40% alcohol\]), or positive alcohol breath test at screening. * Use of soft drugs (such as marijuana) within 3 months of the screening visit or hard drugs (such as cocaine, phencyclidine (PCP) and crack) within 1 year of the screening visit or positive urine drug screen at screening. * History of allergic reactions to heparin, levetiracetam, or other related drugs. * Use of any drugs known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; examples of inhibitors: antidepressants, cimetidine, diltiazem, macrolides, imidazoles, neuroleptics, verapamil, fluoroquinolones, antihistamines) within 30 days prior to the administration of the study medication. * Use of an investigational drug or participation in an investigational study within 30 days prior to dosing. * Clinically significant history or presence of any gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug. * Any clinically significant history or presence of neurological, endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric or metabolic disease. * Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products) including natural food supplements, vitamins, garlic as a supplement) within 7 days prior to administration of study medication, except for topical products without systemic absorption. * Difficulty to swallow study medication. * Smoking more than 25 cigarettes per day. * Any food allergy, intolerance, restriction, or special diet, that, in the opinion of the Medical Sub-Investigator could contraindicate the subject's participation in this study. * A depot injection or an implant of an drug within 6 months prior to administration of study medication. * Donation of plasma (500 mL) within 30 days prior to drug administration. Donation or loss of whole blood (excluding the volume of blood that will be drawn during the screening procedures of this study) prior to administration of the study medication as follows: * 50 mL to 500 mL of whole blood within 30 days * more than 500 mL of whole blood within 56 days.+ * Difficulty fasting or consuming the standard meals. * Intolerance to venipunctures. * Clinically significant history of renal, hepatic, or cardiovascular disease, tuberculosis, epilepsy, asthma, diabetes, psychosis or glaucoma will not be eligible for this study. * Positive urine pregnancy test at screening. * Breast feeding subjects.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 36 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 36 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | Blood samples collected over 36 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam (Test) First Levetiracetam 750 mg Tablet (test) dosed in first period followed by Keppra® 750 mg Tablet (reference) dosed in second period | 11 |
| Keppra® (Reference) First Keppra® 750 mg Tablet (reference) dosed in first period followed by Levetiracetam 750 mg Tablet (test) dosed in second period | 11 |
| Total | 22 |
Baseline characteristics
| Characteristic | Levetiracetam (Test) First | Keppra® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 11 Participants | 22 Participants |
| Race/Ethnicity, Customized Caucasian | 11 Participants | 11 Participants | 22 Participants |
| Region of Enrollment Canada | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 186.758 mcg*h/mL | Standard Deviation 30.682 |
| Keppra® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 186.899 mcg*h/mL | Standard Deviation 31.029 |
90% CI: [97.6, 102]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 176.267 mcg*h/mL | Standard Deviation 31.911 |
| Keppra® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 174.729 mcg*h/mL | Standard Deviation 33.259 |
90% CI: [98.1, 104]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 36 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | Cmax - Maximum Observed Concentration | 19.635 mcg/mL | Standard Deviation 3.854 |
| Keppra® | Cmax - Maximum Observed Concentration | 20.054 mcg/mL | Standard Deviation 4.125 |
90% CI: [94.5, 102]