Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the rate and extent of absorption of lamotrigine 200 mg tablets (test) versus Lamictal® (reference) administered as 1 x 200 mg tablet under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGLamotrigine
200 mg Tablet
DRUGLamictal®
200 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
* Subjects will be females and/or males, non-smokers, 18 years of age and older. * Female Subjects will be post-menopausal or surgically sterilized. * Post-menopausal status is defined as absence of menses for the past 12 months, * Sterile status is defined as hysterectomy, bilateral oophorectomy or tubal ligation at least 6 months ago.
Exclusion criteria
Subjects to whom any of the following applies will be excluded from the study: * Clinically significant illnesses within 4 weeks of the administration of study medication. * Clinically significant surgery within 4 weeks prior to the administration of the study medication. * Any clinically significant abnormality found during medical screening. * Subjects with a history of renal, hepatic or cardiovascular disease, tuberculosis, epilepsy, asthma, diabetes, psychosis or glaucoma will not be eligible for this study. * Any reason which, in the opinion of the medical subinvestigator, would prevent the subject from participating in the study. * Abnormal laboratory tests judged clinically significant. * Positive urine drug screen at screening. * 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) at screening. * Subjects with BMI ≥30.0. * History of significant alcohol abuse within six months of the screening visit or any indication of the regular use of more than two units of alcohol per day (1 Unit = 150 mL of wine or 360 mL of beer or 45 mL of alcohol 40%). * History of drug abuse or use of illegal drugs: 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. * Any food allergy, intolerance, restriction or special diet that, in the opinion of the medical subinvestigator, contraindicates the subject's participation in this study. * History of allergic reactions to lamotrigine. * Use of any drugs known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, rifampin/rifabutin; examples of inhibitors: antidepressants, cimetidine, diltiazem, erythromycin, ketoconazole, MAO inhibitors, neuroleptics, verapamil, quinidine, valproic acid, use of an investigational drug or participation on an investigation study within 30 days prior to the administration of the study medication. * Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products )including natural products, vitamins, garlic as a supplement) within 7 days prior to administration of study medication, except for topical products without systemic absorption. * Subjects who have had a depot injection or an implant of any drug 3 months prior to administration of study medication. * Donation of plasma (500 mL) within 7 days. Donation or loss of whole blood prior to administration of the study medication as follows: * Less than 300 mL of whole blood within 30 days or * 300 mL to 500 mL of whole blood within 45 days or * more than 500 mL of whole blood within 56 days. * Positive alcohol breath test at screening. * Subjects who have used tobacco in any form within the 90 days preceding study drug administration. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 120 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 120 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 120 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lamotrigine (Test) First Lamotrigine 200 mg Tablet (test) dosed in first period followed by Lamictal® 200 mg Tablet (reference) dosed in second period | 16 |
| Lamictal® (Reference) First Lamictal® 200 mg Tablet (reference) dosed in first period followed by Lamotrigine 200 mg Tablet (test) dosed in second period | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Lamotrigine (Test) First | Lamictal® (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 | 16 Participants | 16 Participants | 32 Participants |
| Race/Ethnicity, Customized American Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 16 Participants | 15 Participants | 31 Participants |
| Region of Enrollment Canada | 16 participants | 16 participants | 32 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 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 120 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 131594.33 ng*h/mL | Standard Deviation 53082.11 |
| Lamictal® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 126071.99 ng*h/mL | Standard Deviation 46199.29 |
90% CI: [100.75, 105.93]
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 120 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 113029.41 ng*h/mL | Standard Deviation 34347.88 |
| Lamictal® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 110324.30 ng*h/mL | Standard Deviation 32081.83 |
90% CI: [100.06, 104.26]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 120 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | Cmax - Maximum Observed Concentration | 2518.00 ng/mL | Standard Deviation 352.74 |
| Lamictal® | Cmax - Maximum Observed Concentration | 2442.49 ng/mL | Standard Deviation 369.68 |
90% CI: [100.78, 105.73]