Clinical trial NCT00987558: Effect of Repeated Administration of Eslicarbazepine Acetate on the Pharmacokinetics of Simvastatin in Healthy Subjects
Official title: Effect of Repeated Administration of Eslicarbazepine Acetate on the Pharmacokinetics of Simvastatin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epilepsy
Keywords: Eslicarbazepine acetate
simvastatin
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2009-10-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Simvastatin Cmax (Maximum Plasma Concentration)
timeFrame: Day 1 and Day 14
measure: Simvastatin Tmax (Time of Occurrence of Cmax)
timeFrame: Day 1 and Day 14
measure: Simvastatin AUC0-t
timeFrame: Day 1 and Day 14
measure: Simvastatin AUC0-∞ (AUC From Time Zero to Infinity)
timeFrame: Day 1 and Day 14
Secondary outcomes:
Other outcomes:
Locations:
city: Rennes
country: France
facility: Biotrial, 7-9 rue Jean-Louis Bertrand
Study officials:
affiliation: Biotrial, 7-9, rue Jean-Louis Bertrand, F-35000 Rennes, France
name: Marie Claude Homery, MD
role: PRINCIPAL_INVESTIGATOR
References: