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

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.

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.

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.