effect of repeated administration of eslicarbazepine acetate on the pharmacokinetics of simvastatin in healthy subjects

Conditions: Epilepsy

Summary: the primary objective was to investigate whether multiple-dose administration of esl 800 mg once daily affects the pharmacokinetics of simvastatin, a substrate of cyp34a.

this was a single centre, two-way crossover, randomised, open-label study in 24 healthy volunteers. the volunteers will receive an oral single-dose of simvastatin 80 mg on two occasions - once administered alone and once after treatment with an oral once-daily dose of 800 mg of esl for 14 days -, separated by a washout period of 3 weeks or more

Eligibility criteria:
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 ecg; negative tests for hbsag, anti-hcvab and 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 uses one of the following methods of contraception: double barrier method: 1 male barrier method \[male condom\] plus 1 female barrier method (diaphragm, spermicide, or intrauterine device); * if female, has 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 * clinically relevant surgical history; * history of relevant atopy or any drug hypersensitivity (including known hypersensitivity to esl or other carboxamide derivatives, simvastatin or other statins or any of its excipients * history of fibromyalgia, myopathy, rhabdomyolysis or unexplained muscle pain * second or third-degree atrioventricular blockade not corrected with a pacemaker or any other clinically significant abnormality in the 12-lead electrocardiogram (ecg) as determined by the investigator * history of alcoholism or drug abuse * consume more than 14 units 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 * have donated or received any blood or blood products within the 3 months prior to screening * vegetarians, vegans or have other medical dietary restrictions * cannot communicate reliably with the investigator * unlikely to co-operate with the requirements of the study * unwilling or unable to give written informed consent * if female, is pregnant or breast-feeding * if female, is of childbearing potential and does not use an approved effective contraceptive method (double-barrier method: 1 male barrier method \[male condom\] plus 1 female barrier method (diaphragm, spermicide, or intra-uterine device) or uses hormonal contraceptives * have received an investigational drug within 3 months of screening or is currently participating in another study

Keywords: eslicarbazepine acetate simvastatin