Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study was to compare the rate and extent of absorption of topiramate 25 mg capsules (test) versus Topamax® (reference) administered as 2 x 25 mg capsules under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
Topiramate Capsules, 2 x 25 mg
Topamax® Capsules, 2 x 25 mg
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 or older * Subjects should read, sign and date an Informed Consent Form prior to any study procedures. * Female subjects will be post-menopausal or surgically sterilized. * Post menopausal status is defined as absence of menses for the past 12 months or bilateral oophorectomy at least 6 months ago or hysterectomy with bilateral oophorectomy at least 6 months ago. * Sterile status is defined as hysterectomy, bilateral oophorectomy or tubal ligation aat least 6 months ago.
Exclusion criteria
* 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 history or presence of significant neurological, hepatic, renal, endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric or metabolic disease. * Any clinically significant abnormality found during medical screening. * Abnormal laboratory tests judged clinically significant. * Positive urine drug screen at screening. * Positive alcohol breath test at screening. * Subjects who use tobacco in any form will not be eligible to participate in this study. Three months abstinence is required. * Positive testing for hepatitis B, hepatitis C or HIV at screening. * ECG or vital sign abnormalities (clinically significant). * Subjects with BMI greater than or equal to 30.0. * History of significant alcohol abuse within 6 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 subjects participation in this study. * History of allergic reactions to topiramate. * Use of any drugs known to induce or inhibit hepatic drug metabolism, 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 within 7 days prior to administration of study medication, except for topical products without systemic absorption. * Donation of plasma (500 mL) within 7 days or donation or significant loss of whole blood (500 mL) within 56 days prior to administration of the study medication. * Any reason which, in the opinion of the medical subinvestigator, would prevent the subject from participating in the study. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 168 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 168 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 168 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate (Test) First Topiramate Capsules, 2 x 25 mg (test) dosed in first period followed by Topamax® Capsules, 2 x 25 mg (reference) dosed in second period | 12 |
| Topamax® (Reference) First Topamax® Capsules, 2 x 25 mg (reference) dosed in first period followed by Topiramate Capsules,2 x 25 mg (test) dosed in second period | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Topiramate (Test) First | Topamax® (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 | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized American Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Caucasian | 9 Participants | 9 Participants | 18 Participants |
| Region of Enrollment Canada | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 9 Participants | 7 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 168 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate (Test) | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 37553.92 ng*hr/mL | Standard Deviation 7995.76 |
| Topamax® (Reference) | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 37985.24 ng*hr/mL | Standard Deviation 7790.42 |
90% CI: [97.6, 102.72]
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 168 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate (Test) | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 32844.22 ng*hr/mL | Standard Deviation 7746.34 |
| Topamax® (Reference) | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 32915.59 ng*hr/mL | Standard Deviation 7694.56 |
90% CI: [99.01, 104.12]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 168 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate (Test) | Cmax - Maximum Observed Concentration | 799.78 ng/mL | Standard Deviation 263.94 |
| Topamax® (Reference) | Cmax - Maximum Observed Concentration | 810.40 ng/mL | Standard Deviation 255.47 |
90% CI: [94.27, 105.03]