Pharmacokinetic Interaction Study Between Eslicarbazepine Acetate and Carbamazepine

Study Overview
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Brief Summary
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Open-label study in two parallel groups of 20 healthy subjects each. Group A assessed the effect of CBZ on ESL pharmacokinetics, and Group B assessed the effect of ESL on CBZ pharmacokinetics.

Detailed Description
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Open-label study in two parallel groups of 20 healthy subjects each. Group A assessed the effect of CBZ on ESL pharmacokinetics, and Group B assessed the effect of ESL on CBZ pharmacokinetics. Each patient participated in the study for approximately 9 weeks. The clinical portion of the study was completed in approximately 3 months. Subjects received the treatments during 35 days.

Official Title
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Pharmacokinetic Interaction Study Between Eslicarbazepine Acetate and Carbamazepine in Healthy Subject

Conditions
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Epilepsy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged 18 to 45 years inclusive; Body mass index (BMI) between 18 and 30 kg/m2 inclusive; Healthy as determined by pre-study medical history, physical examination, vital signs, and 12-lead electrocardiogram (ECG); negative tests for Hepatitis B surface Antigen (HBsAg), anti-HCVAb and Human Immunodeficiency Virus (HIV)-1 and HIV-2 Ab at screening; Clinical laboratory test results clinically acceptable at screening and admission to each treatment period; Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period; Non-smokers or ex-smokers; Able and willing to give written informed consent; If female, not of childbearing potential by reason of surgery or, if of childbearing potential, she used a double-barrier method of contraception: 1 male barrier method [male condom] plus 1 female barrier method (diaphragm, spermicide, or intrauterine device); If female, had a negative urine pregnancy test at screening and admission to each treatment period. Exclusion Criteria: 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; have a clinically relevant surgical history; History of relevant atopy or any drug hypersensitivity (including known hypersensitivity to ESL or other carboxamide derivatives [e.g., carbamazepine, oxcarbazepine] or any of its excipients; known hypersensitivity to drugs structurally related to carbamazepine [e.g.: tricyclic antidepressants] or any of its excipients); Second or third-degree atrioventricular blockade not corrected with a pace-maker or any other clinically significant abnormality in the 12-lead ECG as determined by the investigator; History of alcoholism or drug abuse; Consumed more than 14 units1 of alcohol a week; Significant infection or known inflammatory process on screening or admission to each treatment period; Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period; Use of medicines within two weeks of admission to first period that may affect the safety or other study assessments, in the investigator's opinion; Had donated or received any blood or blood products within the 3 months prior to screening; Vegetarians, vegans or have other medical dietary restrictions; Could not communicate reliably with the investigator; was unlikely to co-operate with the requirements of the study; Unwilling or unable to give written informed consent; If female, was pregnant or breast-feeding; If female, was of childbearing potential and did not use an accepted effective contraceptive method or used hormonal contraceptives; Had received an investigational drug within 3 months of screening or was currently participating in another study.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Day 1 to Day 8 - BIA 2-093 800 mg Day 9 to Day 14 - BIA 2-093 800 mg + CBZ 200 mg Day 15 to Day 22 - BIA 2-093 800 mg + CBZ 400 mg Day 23 to Day 35 - BIA 2-093 800 mg + CBZ 400 mg twice-daily | Drug: BIA 2-093<br> <br> * Other names: ESL;Drug: Carbamazepine<br> <br> * Other names: CBZ;|
| Experimental: Group B<br>Day 1 to Day 8 - CBZ 200 mg Day 9 to Day 14 - CBZ 400 mg Day 15 to Day 29 - CBZ 400 mg twice-daily Day 30 to Day 35 - BIA 2-093 800 mg + CBZ 400 mg twice-daily | Drug: BIA 2-093<br> <br> * Other names: ESL;Drug: Carbamazepine<br> <br> * Other names: CBZ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (BIA 2-093) - the Maximum Plasma Concentration | Reference - Day 7 following once-daily oral administration of ESL 800 mg Test - Day 35 following once-daily oral administration of ESL 800 mg | Day 7 to 35 | 
| Cmax (CBZ) - the Maximum Plasma Concentration | Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg | Day 28 to 35 | 
| Cmax (CBZE) - the Maximum Plasma Concentration | Reference - Day 28 following twice-daily oral administration of CBZ 400 mg twice-daily Test - Day 35 following twice-daily oral administration of CBZ 400 mg twice-daily CBZE - carbamazepine-epoxide is the active metabolite of CBZ | Day 28 to 35 | 
| AUC0-t (BIA 2-093) - Area Under the Curve to Last Measurable Concentration for BIA 2-093 | Reference - Day 7 following once-daily oral administration of ESL 800 mg Test - Day 35 following once-daily oral administration of ESL 800 mg | Day 7 to 35 | 
| AUC0-t (CBZ) - Area Under the Curve to Last Measurable Concentration for CBZ | Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg | Day 28 to 35 | 
| AUC0-t (CBZE) - Area Under the Curve to Last Measurable Concentration for CBZE | Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg CBZE - carbamazepine-epoxide is the active metabolite of CBZ | Day 28 to 35 |