Oxcarbazepine 600 mg Tablets Under Non-Fasting Conditions

Study Overview
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Brief Summary
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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
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Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods

Official Title
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Randomized, Open-Label, 2-Way Crossover, Bioequivalence Study of Oxcarbazepine 600 mg Tablet and Trileptal® Following a 600 mg Dose in Healthy Subjects Under Fed Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Oxcarbazepine
* Drug: Trileptal®


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxcarbazepine<br>Oxcarbazepine 600 mg Tablet (test) dosed in first period followed by Trileptal® 600 mg Tablet (reference) dosed in second period | Drug: Oxcarbazepine<br>* 600 mg Tablet<br>|
| Active Comparator: Trileptal®<br>Trileptal® 600 mg Tablet (reference) dosed in first period followed by Oxcarbazepine 600 mg Tablet (test) dosed in second period | Drug: Trileptal®<br>* 600 mg Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Observed Concentration - Oxcarbazepine in Plasma | Bioequivalence based on Cmax | Blood samples collected over 48 hour period | 
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Oxcarbazepine | Bioequivalence based on AUC0-inf | Blood samples collected over 48 hour period | 
| 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 | Blood samples collected over 48 hour period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - 10-hydroxy-carbazepine in Plasma | Informational Purposes Only | Blood samples collected over 48 hour period | 
| AUC0-inf - 10-Hydroxy-Carbazepine Metabolite | Informational Purposes Only | Blood samples collected over 48 hour period | 
| AUC0-t - 10-Hydroxy-Carbazepine Metabolite | Informational Purposes Only | Blood samples collected over 48 hour period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Healthy Subjects