Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to evaluate the comparative bioavailability between Oxcarbazepine 600 mg Tablets (test) and Trileptal® 600 mg Tablets (reference) after a single-dose in healthy subjects under fasting 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
* Healthy, non-smoking male and female subjects, 18 years of age or older. * BMI greater than or equal to 19 and less than or equal to 30. * Negative for: * HIV. * Hepatitis B surface antigen and Hepatitis C antibody. * Using drugs of abuse test (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone). * Urine cotinine test * Serum HCG consistent with pregnancy (females only) * No significant diseases or clinically significant findings in a physical examination. * No clinically significant abnormal laboratory values. * No clinically significant findings in vital signs measurements and a 12-lead electrocardiogram (ECG). * Be informed of the nature of the study and given written consent prior to receiving any study procedure. * Females who participate in this study are: * unable to have children (e.g. post-menopausal, tubal ligation, hysterectomy or, * willing to remain abstinent \[not engage in sexual intercourse\] or, * willing to use an effective method of double-barrier birth control \[partner using condom and female using diaphragm, contraceptive sponge, spermicide or IUD\]. * Females who participate in this study are not pregnant and/or non-lactating.
Exclusion criteria
* Known history or presence of any clinically significant medical condition. * Known or suspected carcinoma. * Known history or presence of: * Hypersensitivity or idiosyncratic reaction to oxcarbazepine and/or any other drug substances with similar activity. * Alcoholism within the last 12 months. * Drug dependence and/or substance abuse. * Use of tobacco or nicotine-containing products within the last 6 months. * On a special diet within 4 weeks prior to drug administration (e.g. liquid, protein, raw food diet). * Participated in another clinical trial or received and investigational product within 30 days prior to drug administration. * Donated up to 250 mL of blood within the previous 30 days OR Donated from 251 to 500 mL of blood in the previous 45 days OR Donated more than 500 mL of blood in the previous 56 days (based on the Canadian Blood Services guideline for blood donation. * Females taking oral or transdermal hormonal contraceptives within 14 days preceding period 1 dosing. * Females having taken implanted or injected hormonal contraceptives within 6 months prior to period 1 dosing. * Requirement of any medication (prescription, hormonal contraceptive and/or over-the-counter) on a routine basis, with the exception of nutritional supplements and/or occasional use of common analgesics. * Difficulty fasting or consuming the standard meals.
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 | Results of Metabolite for Informational Purposes Only |
| AUC0-inf - 10-hydroxy-carbazepine Metabolite | Blood samples collected over 48 hour period | Results of Metabolite for informational purposes only |
| AUC0-t - 10-hydroxy-carbazepine Metabolite | Blood samples collected over 48 hour period | Results of metabolite for 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 | 30 |
| Trileptal® (Reference) First Trileptal® 600 mg Tablet (reference) dosed in first period followed by Oxcarbazepine 600 mg Tablet (test) dosed in second period | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention | Withdrawal by Subject | 1 | 0 |
| Washout: One Week | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Oxcarbazepine (Test) First | Trileptal® (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 | 60 Participants | 30 Participants | 30 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants | 5 Participants | 7 Participants |
| Race/Ethnicity, Customized Black | 14 Participants | 10 Participants | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 34 Participants | 15 Participants | 19 Participants |
| Region of Enrollment Canada | 60 participants | 30 participants | 30 participants |
| Sex: Female, Male Female | 22 Participants | 10 Participants | 12 Participants |
| Sex: Female, Male Male | 38 Participants | 20 Participants | 18 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. AUC0-inf was not able to be estimated from all data sets.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxcarbazepine | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Oxcarbazepine | 5873.1 ng*h/mL | Standard Deviation 1598.8 |
| Trileptal® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Oxcarbazepine | 5711.7 ng*h/mL | Standard Deviation 1472.3 |
90% CI: [99.19, 106.01]
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 | 5309.5 ng*h/mL | Standard Deviation 1598.1 |
| Trileptal® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Oxcarbazepine | 5176.8 ng*h/mL | Standard Deviation 1494.4 |
90% CI: [98.78, 105.71]
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 | 1630.3 ng/mL | Standard Deviation 662.6 |
| Trileptal® | Cmax - Maximum Observed Concentration - Oxcarbazepine in Plasma | 1620.2 ng/mL | Standard Deviation 644.3 |
90% CI: [88.98, 109]
Secondary
AUC0-inf - 10-hydroxy-carbazepine Metabolite
Results of Metabolite for 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 | 173770 ng*h/mL | Standard Deviation 37809 |
| Trileptal® | AUC0-inf - 10-hydroxy-carbazepine Metabolite | 174424 ng*h/mL | Standard Deviation 44645 |
90% CI: [97.75, 102.18]
Secondary
AUC0-t - 10-hydroxy-carbazepine Metabolite
Results of metabolite for 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 | 157372 ng*h/mL | Standard Deviation 29483 |
| Trileptal® | AUC0-t - 10-hydroxy-carbazepine Metabolite | 157542 ng*h/mL | Standard Deviation 31906 |
90% CI: [97.5, 102.15]
Secondary
Cmax - 10-hydroxy-carbazepine in Plasma
Results of Metabolite for 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 | 7119 ng/mL | Standard Deviation 1663 |
| Trileptal® | Cmax - 10-hydroxy-carbazepine in Plasma | 7004 ng/mL | Standard Deviation 1410 |
90% CI: [97.03, 104.65]