the effect of bia 2-093 on the steady-state pharmacokinetic profile of phenytoin in patients

Conditions: Epilepsy

Summary: 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.

Eligibility criteria:
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.

Keywords: anticonvulsant, bia 2-093