The Effect of BIA 2-093 on the Steady-state Pharmacokinetic Profile of Phenytoin in Patients

Study Overview
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Brief Summary
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The purpose of this study is determine the interaction of eslicarbazepine acetate (ESL, BIA 2-093) on the steadystate pharmacokinetics of phenytoin in patients and to evaluate the tolerability and safety of ESL administered concomitantly with phenytoin in patients.

Detailed Description
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This study was planned as a single-dose, open label phase (Phase A) followed by a multiple-dose, double-blind, randomised, placebo-controlled, two-way crossover phase (Phase B) study in patients taking phenytoin. Phase B consisted of two 14-day treatment periods separated by a washout period of 10 to 15 days. Subjects continued their usual phenytoin scheme and received a single dose of ESL 1200 mg (Phase A) and either ESL (600 mg from Day 1 to 7 and 1200 mg from Day 8 to 14) or matching placebo once-daily for 14 days in each period. The study was prematurely terminated due to impossibility of recruiting the planned number of patients. Only 4 patients were admitted and this was considered a too small sample size to allow a reliable assessment of the potential interaction between ESL and phenytoin. Therefore, no pharmacokinetic evaluation was performed.

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Eslicarbazepine acetate
* Drug: phenytoin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged between 18 and 65 years, inclusive. Subjects who were on an established regimen of phenytoin monotherapy, which had been stable for at least 3 months. Subjects who had clinical laboratory tests acceptable to the Investigator. Subjects who were negative for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) and human immunodeficiency viruses (HIV-1 and HIV-2) Ab tests at screening. Subjects who were negative for alcohol and drugs of abuse at screening. Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day. Subjects who were able and willing to gave written informed consent. (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier or intrauterine device. (If female) She had a negative pregnancy test at screening. Exclusion Criteria: Subjects who did not conform to the above inclusion criteria. Subjects who had a clinically relevant history or presence of any disease that may interfere with the pharmacokinetics or pharmacodynamics of the Investigational Products, or may affect its safety. Subjects who had a history of relevant drug hypersensitivity. Subjects who had a history of alcoholism or drug abuse in the last 2 years. Subjects who consumed more than 21 units of alcohol a week. Subjects who had one of the following findings on the electrocardiogram (ECG): sinus bradycardia, sinoatrial block, atrioventricular block of any degree. Subjects who had a significant infection or known inflammatory process on screening and/or admission. Subjects who had acute gastrointestinal symptoms at the time of screening and/or admission (e.g., nausea, vomiting, diarrhoea, heartburn). Subjects who had used any drugs (other than phenytoin) that may affect the pharmacokinetic profile of the investigational products within 2 weeks of first dosing. Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of their first admission to this study. Subjects who had previously received ESL. Subjects who had donated and/or received any blood or blood products within the previous 3 months prior to screening. Subjects who were vegetarians, vegans and/or have medical dietary restrictions. Subjects who cannot 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 gave written informed consent. (If female) She was pregnant or breast-feeding. (If female) She was of childbearing potential and she did not use an approved effective contraceptive method.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eslicarbazepine acetate<br>ESL 600 mg tablets | Drug: Eslicarbazepine acetate<br>* Tablets containing ESL 600 mg<br>* Other names: BIA 2-093;|
| Active Comparator: phenytoin<br>Hidantina® 100 mg tablets | Drug: phenytoin<br>* Hidantina® tablets containing 100 mg of phenytoin<br>* Other names: Hidantina® 100 mg tablets;|
| Placebo Comparator: Placebo<br>Placebo tablets | Drug: Placebo<br>* Tablets containing matching placebo<br>* Other names: Placebo tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events reported | Number of the adverse events reported | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anticonvulsant, BIA 2-093