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 oxcarbazepine tablets and Trileptal® tablets administered as a 1 x 600 mg dose under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGOxcarbazepine
600 mg Tablet
DRUGTrileptal®
600 mg Tablet
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female, smoker or non-smoker, 18 years of age and older. * BMI greater than or equal to 19.0 and less than or equal to 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 90mmHg; or heart rate less than 50 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 14 units of alcohol per \[1 Unit = 150 mL of wine or 360 mL of beer or 45 mL of 40% alcohol\], 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 prior to the screening visit or positive urine drug screen at screening. * History of allergic reactions to heparin, oxcarbazepine, carbamazepine, 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 (SSRI), 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 on an investigation study within 30 days prior to dosing. * Clinically significant history or presence of any gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel disease), 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 or 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 any drug within 3 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 300 mL of whole blood within 30 days or * 301 mL to 500 mL of whole blood within 45 days or * more than 500 mL of whole blood within 56 days. * Consumption of food or beverages containing grapefruit (e.g. fresh, canned or frozen) within 7 days prior to administration of the study medication. * History or presence of atreoventricular (AV) block. * Difficulty fasting or consuming the standard meals. * Intolerance to venipunctures. * Clinically significant history of renal, hepatic, or cardiovascular, tuberculosis, epilepsy, asthma, diabetes, psychosis, or glaucoma will not be eligible for this study. * Positive urine pregnancy test at screening. * Breast-feeding subject. * Female subjects of child-bearing potential having unprotected sexual intercourse with any non-sterile male partner within 14 days prior to study drug administration. Acceptable methods of contraception: * Intra-uterine contraceptive device (placed at least 4 weeks prior to study drug administration. * Condom or diaphragm + spermicide.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration - Oxcarbazepine in Plasma | Blood samples collected over 48 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Oxcarbazepine | Blood samples collected over 48 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) - Oxcarbazepine | Blood samples collected over 48 hour period | Bioequivalence based on AUC0-t |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - 10-hydroxy-carbazepine in Plasma | Blood samples collected over 48 hour period | Informational Purposes Only |
| AUC0-inf - 10-Hydroxy-Carbazepine Metabolite | Blood samples collected over 48 hour period | Informational Purposes Only |
| AUC0-t - 10-Hydroxy-Carbazepine Metabolite | Blood samples collected over 48 hour period | Informational Purposes Only |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxcarbazepine (Test) First Oxcarbazepine 600 mg Tablet (test) dosed in first period followed by Trileptal® 600 mg Tablet (reference) dosed in second period | 60 |
| Trileptal® (Reference) First Trileptal® 600 mg Tablet (reference) dosed in first period followed by Oxcarbazepine 600 mg Tablet (test) dosed in second period | 60 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 0 | 1 |
| First Intervention | bad veins | 1 | 0 |
| Washout: One Week | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Oxcarbazepine (Test) First | Trileptal® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 56 Participants | 114 Participants |
| Race/Ethnicity, Customized American Hispanic | 6 Participants | 7 Participants | 13 Participants |
| Race/Ethnicity, Customized Black | 6 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Caucasian | 48 Participants | 51 Participants | 99 Participants |
| Region of Enrollment Canada | 60 participants | 60 participants | 120 participants |
| Sex: Female, Male Female | 25 Participants | 27 Participants | 52 Participants |
| Sex: Female, Male Male | 35 Participants | 33 Participants | 68 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Oxcarbazepine
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxcarbazepine | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Oxcarbazepine | 9679.79 ng*h/mL | Standard Deviation 2371.03 |
| Trileptal® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Oxcarbazepine | 9772.18 ng*h/mL | Standard Deviation 2350.44 |
90% CI: [96.59, 100.66]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Oxcarbazepine
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxcarbazepine | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Oxcarbazepine | 9445.55 ng*h/mL | Standard Deviation 2327.24 |
| Trileptal® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Oxcarbazepine | 9539.53 ng*h/mL | Standard Deviation 2293.33 |
90% CI: [96.71, 100.8]
Primary
Cmax - Maximum Observed Concentration - Oxcarbazepine in Plasma
Bioequivalence based on Cmax
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxcarbazepine | Cmax - Maximum Observed Concentration - Oxcarbazepine in Plasma | 3537.63 ng/mL | Standard Deviation 1333.09 |
| Trileptal® | Cmax - Maximum Observed Concentration - Oxcarbazepine in Plasma | 3820.31 ng/mL | Standard Deviation 1357.08 |
90% CI: [85.47, 96.6]
Secondary
AUC0-inf - 10-Hydroxy-Carbazepine Metabolite
Informational Purposes Only
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxcarbazepine | AUC0-inf - 10-Hydroxy-Carbazepine Metabolite | 197864.34 ng*h/mL | Standard Deviation 47069.89 |
| Trileptal® | AUC0-inf - 10-Hydroxy-Carbazepine Metabolite | 196607.20 ng*h/mL | Standard Deviation 43337.72 |
90% CI: [98.96, 101.64]
Secondary
AUC0-t - 10-Hydroxy-Carbazepine Metabolite
Informational Purposes Only
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxcarbazepine | AUC0-t - 10-Hydroxy-Carbazepine Metabolite | 179002.40 ng*h/mL | Standard Deviation 39157.51 |
| Trileptal® | AUC0-t - 10-Hydroxy-Carbazepine Metabolite | 177979.76 ng*h/mL | Standard Deviation 35506.55 |
90% CI: [98.91, 101.27]
Secondary
Cmax - 10-hydroxy-carbazepine in Plasma
Informational Purposes Only
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxcarbazepine | Cmax - 10-hydroxy-carbazepine in Plasma | 9349.83 ng/mL | Standard Deviation 1739.68 |
| Trileptal® | Cmax - 10-hydroxy-carbazepine in Plasma | 9517.52 ng/mL | Standard Deviation 2034.08 |
90% CI: [95.66, 100.48]