Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the rate and extent of absorption of lamotrigine 25 mg chewable dispersible tablets (test) versus Lamictal® (reference) administered as 2 x 25 mg chewable dispersible tablets under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
2 x 25 mg, single-dose fasting
2 x 25 mg, single-dose fasting
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 or hysterectomy with bilateral oophorectomy at least 6 months ago. * Sterile status is defined as hysterectomy, bilateral oophorectomy or tubal ligation at least 6 months ago.
Exclusion criteria
* Clinically significant illnesses within 4 weeks of the administration of the 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 sub-investigator, 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 (PVP) and crack) within 1 year of the screening visit. * Any food allergy, intolerance, restriction or special diet that, in the opinion of the medical sub-investigator, contraindicates the subject's participation in this study. * History of allergic reactions to lamotrigine. * Use of any drugs known to induce or inhibit 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 in an investigational study within 30 days prior to 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 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. * Subjects who have dentures or braces. * Donation of plasma (500 mL) within 7 days. Donation or loss of whole blood prior to administration of the study medication as follow: less than 300 mL of whole blood within 30 days; 300 mL to 500 mL of whole blood within 45 days; 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 90 days preceding study drug administration. * Female subjects: breast-feeding subjects. * Female subjects: positive urine pregnancy test at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 120 hour period | Bioequivalence basd 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 2 x 25 mg Chewable Tablet (test) dosed in first period followed by Lamictal® 2 x 25 mg Chewable Tablet (reference) dosed in second period | 16 |
| Lamictal® (Reference) First Lamictal® 2 x 25 mg Chewable Tablet (reference) dosed in first period followed by Lamotrigine 2 x 25 mg Chewable Tablet (test) dosed in second period | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout | Protocol Violation | 1 | 0 |
| Washout | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Lamotrigine (Test) First | Lamictal® (Reference) First |
|---|---|---|---|
| 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 | 32 Participants | 16 Participants | 16 Participants |
| Race/Ethnicity, Customized American Hispanic | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 25 Participants | 13 Participants | 12 Participants |
| Region of Enrollment Canada | 32 participants | 16 participants | 16 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 31 Participants | 15 Participants | 16 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: Two subjects did not complete the study, and there was an issue with dosing of one subject (the whole tablet was not consumed for one of the periods) therefore there are 29 data sets that 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) | 34541.03 ng*h/mL | Standard Deviation 14354.41 |
| Lamictal® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 33498.85 ng*h/mL | Standard Deviation 12316.96 |
90% CI: [99.09, 104.55]
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: Two subjects did not complete the study, and there was an issue with dosing of one subject (the whole tablet was not consumed for one of the periods) therefore there are 29 data sets that 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) | 28843.06 ng/mL | Standard Deviation 6866.12 |
| Lamictal® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 28923.66 ng/mL | Standard Deviation 7355.31 |
90% CI: [97.4, 102.55]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence basd on Cmax
Time frame: Blood samples collected over 120 hour period
Population: Two subjects did not complete the study, and there was an issue with dosing of one subject (the whole tablet was not consumed for one of the periods) therefore there are 29 data sets that were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | Cmax - Maximum Observed Concentration | 713.46 ng/mL | Standard Deviation 95.02 |
| Lamictal® | Cmax - Maximum Observed Concentration | 709.97 ng/mL | Standard Deviation 84.37 |
90% CI: [97.82, 102.85]