Steady-state Pharmacokinetics of BIA 2-093 and Oxcarbazepine in Healthy Volunteers

Study Overview
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Brief Summary
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To investigate the steady-state pharmacokinetics of once-daily and twice-daily regimens of BIA 2-093 and twice-daily regimen of Oxcarbazepine (Trileptal®) in healthy subjects and to assess the tolerability of such regimens in healthy subjects.

Detailed Description
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Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers. The study consisted of three 8-day treatment periods separated by washout periods of 10-15 days. On each of the treatment periods the volunteers received either a daily oral dose of BIA 2-093 900 mg once-daily (od), BIA 2-093 450 mg twice-daily (bid), or Oxcarbazepine (Trileptal®) 450 mg bid.

Official Title
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Steady-state Pharmacokinetics of BIA 2-093 and Oxcarbazepine in Healthy Volunteers

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: BIA 2-093
* Drug: Oxcarbazepine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects were eligible for entry into the study if they fulfilled the following inclusion criteria: Male or female subjects aged between 18 and 45 years, inclusive. Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive. Subjects who were healthy as determined by pre-study medical history, physical examination, neurological examination, and 12-lead ECG. Subjects who had clinical laboratory tests clinically acceptable. Subjects who were negative for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab tests at screening. Subjects who were negative for alcohol and drugs of abuse at screening and first admission. Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day. Subjects who were able and willing to give written informed consent. If case of female subjects, subjects who were not of childbearing potential by reason of surgery or, if of childbearing potential, who used one of the following methods of contraception: double-barrier, intrauterine device or abstinence. If case of female subjects, subjects who had a negative pregnancy test at screening and first admission. Exclusion Criteria: Subjects who did not conform to the above inclusion criteria. Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders. Subjects who had a clinically relevant surgical history. Subjects who had a clinically relevant family history. Subjects who had a history of relevant atopy. Subjects who had a history of hypersensitivity to carbamazepine or oxcarbazepine or any other relevant drug hypersensitivity. Subjects who had a history of alcoholism or drug abuse. Subjects who consumed more than 14 units of alcohol a week. Subjects who had a significant infection or known inflammatory process on screening and/or first admission. Subjects who had acute gastrointestinal symptoms at the time of screening and/or first admission (e.g., nausea, vomiting, diarrhoea, heartburn). Subjects who had used prescription or over-the-counter medication within two weeks of first admission. Subjects who had used any investigational drug and/or participated in any clinical trial within four months of their first admission. Subjects who had previously received BIA 2-093. Subjects who had donated and/or received any blood or blood products within the previous 4 months prior to screening. Subjects who were vegetarians, vegans and/or have medical dietary restrictions. Subjects who could not communicate reliably with the investigator. Subjects who were unlikely to co-operate with the requirements of the study. Subjects who were unwilling or unable to give written informed consent. In case of female subjects, subjects who were pregnant or breast-feeding. In case of female subjects, subjects who were of childbearing potential and did not use an approved effective contraceptive method or used oral contraceptives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period BIA 2-093 450 mg od - BIA 2-093 450 mg bid - OXC 900 mg bid | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;Drug: Oxcarbazepine<br> <br> * Other names: OXC, Trileptal®;|
| Experimental: Group B<br>BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period BIA 2-093 450 mg bid - OXC 450 mg bid - BIA 2-093 900 mg od | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;Drug: Oxcarbazepine<br> <br> * Other names: OXC, Trileptal®;|
| Experimental: Group C<br>oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period OXC 450 mg bid - BIA 2-093 900 mg od - BIA 2-093 450 mg bid | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;Drug: Oxcarbazepine<br> <br> * Other names: OXC, Trileptal®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Observed Plasma Drug Concentration | Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites: BIA 2-194 BIA 2-195 Oxcarbazepine | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC - Area Under the Plasma Concentration Versus Time Curve | AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites: BIA 2-194 BIA 2-195 Oxcarbazepine | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose | 
| Number of of Subjects Reporting at Least One Adverse Event | Number of of subjects reporting at least one adverse event. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Oxcarbazepine, Eslicarbazepine Acetate, BIA 2-093