Food Effect and Dosage Form Proportionality Study of Eslicarbazepine Acetate

Study Overview
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Brief Summary
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Single-centre, open-label, randomised, gender-balanced, 3-way crossover, 3-period, 3-sequence study in 18 healthy male and female subjects.

Detailed Description
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Single-centre, open-label, randomised, gender-balanced, 3-way crossover, 3-period, 3-sequence study in 18 healthy male and female subjects. The study consisted of 3 periods separated by a washout of 7 days or more between doses. Subjects received a single oral 800 mg dose of eslicarbazepine acetate following a standard meal in one period, and following at least 10 hours of fasting in two periods.

Official Title
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Food Effect and Dosage Form Proportionality Study of Eslicarbazepine Acetate Market Formulation in Healthy Volunteers

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: BIA 2-093


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged between 18 and 55 years, inclusive. Subjects of body mass index (BMI, kg/m2) within the normal range [4], i.e., between 18.50 and 24.99, inclusive. Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, and 12-lead ECG. Subjects who had clinical laboratory test results clinically acceptable at screening and admission to first treatment period. Subjects who had negative tests for HBsAg, anti-HCVAb and anti- HIV-1 and HIV-2 Ab at screening. Subjects who had a negative screen for alcohol and drugs of abuse at screening. Subjects who were non-smokers or ex-smokers who discontinued smoking at least 3 months prior to admission. Subjects who were able and willing to give written informed consent. (If female) She was not of childbearing potential by reason of surgery (hysterectomy or tubal ligation) or, if of childbearing potential, she used one of the following methods of contraception: intrauterine device (by the study subject) + condom (by the partner), diaphragm (by the study subject) + condom (by the partner), or spermicide (by the study subject) + condom (by the partner). (If female) She had a negative urine pregnancy test at screening and admission to each treatment period. Exclusion Criteria: Subjects who did not conform to the above inclusion criteria, or 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 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 used medicines within 2 weeks of first admission that, in the opinion of the investigator, may affect the safety or other study assessments. Subjects who used any investigational drug or participated in any clinical trial within 2 months of their first admission. Subjects who had previously received eslicarbazepine acetate (ESL, BIA 2-093). Subjects who donated or received any blood or blood products within the previous 2 months prior to screening. Subjects who were vegetarians, vegans 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. (If female) She was pregnant or breast-feeding. (If female) She was of childbearing potential and she did not used and approved effective contraceptive method or she used oral contraceptives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: BIA 2-093 800 mg fasting<br>Tablets 800 mg. Administration:Oral. | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;|
| Experimental: BIA 2-093 800 mg fed<br>Tablets 800 mg. Administration:Oral. | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;|
| Experimental: BIA 2-093 400 mg<br>Tablets 2 x 400 mg. Administration:Oral. | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (BIA 2-005) | Cmax (BIA 2-005) - maximum observed plasma drug concentration of BIA 2-005 (BIA 2-093 metabolite) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t (BIA 2-005) | AUC0-t (BIA 2-005) - the area under the plasma concentration-time curve from time zero to the last sampling time at which BIA 2-005 concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule (BIA 2-005 is a BIA 2-093 metabolite) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose. | 
| Tmax (BIA 2-005) | tmax (BIA 2-005) - the time of occurrence of Cmax of BIA 2-005 (BIA 2-005 is a BIA 2-093 metabolite) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose. | 
| AUC0-∞ (BIA 2-005) | AUC0-∞ (BIA 2-005) - the area under the plasma BIA 2-005 concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant; (BIA 2-005 is a BIA 2-093 metabolite) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose. |