Effect of Repeated Administration of Eslicarbazepine Acetate on the Pharmacokinetics of Simvastatin in Healthy Subjects

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Effect of Repeated Administration of Eslicarbazepine Acetate on the Pharmacokinetics of Simvastatin in Healthy Subjects

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Eslicarbazepine acetate
* Drug: Simvastatin


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 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

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence A<br>Simvastatin 80mg treatment period followed by Simvastatin 80 mg + eslicarbazepine acetate 800 mg treatment period | Drug: Eslicarbazepine acetate<br> <br> * Other names: Zebinix;Drug: Simvastatin<br> <br> * Other names: Zocor;|
| Experimental: Treatment Sequence B<br>Simvastatin 80mg + eslicarbazepine acetate 800 mg treatment period followed by Simvastatin 80 mg treatment period | Drug: Eslicarbazepine acetate<br> <br> * Other names: Zebinix;Drug: Simvastatin<br> <br> * Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simvastatin Cmax (Maximum Plasma Concentration) | Simvastatin (Reference) ESL + Simvastatin (Test) | Day 1 and Day 14 | 
| Simvastatin Tmax (Time of Occurrence of Cmax) | Simvastatin (Reference) ESL + Simvastatin (Test) | Day 1 and Day 14 | 
| Simvastatin AUC0-t | AUC0-t - area under the plasma concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification Simvastatin (Reference) ESL + Simvastatin (Test) | Day 1 and Day 14 | 
| Simvastatin AUC0-∞ (AUC From Time Zero to Infinity) | Simvastatin (Reference) ESL + Simvastatin (Test) | Day 1 and Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eslicarbazepine acetate, simvastatin