Effect of Repeated Administration of Eslicarbazepine Acetate on the Pharmacokinetics of Simvastatin in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Simvastatin AUC0-t
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Treatment Sequence A
Simvastatin 80mg treatment period followed by Simvastatin 80 mg + eslicarbazepine acetate 800 mg treatment period
干预措施: Eslicarbazepine acetate (Drug)
Treatment Sequence A
Simvastatin 80mg treatment period followed by Simvastatin 80 mg + eslicarbazepine acetate 800 mg treatment period
干预措施: Simvastatin (Drug)
Treatment Sequence B
Simvastatin 80mg + eslicarbazepine acetate 800 mg treatment period followed by Simvastatin 80 mg treatment period
干预措施: Eslicarbazepine acetate (Drug)
Treatment Sequence B
Simvastatin 80mg + eslicarbazepine acetate 800 mg treatment period followed by Simvastatin 80 mg treatment period
干预措施: Simvastatin (Drug)
结局指标
主要结局
Simvastatin AUC0-t
时间窗: Day 1 and Day 14
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)
Simvastatin Tmax (Time of Occurrence of Cmax)
时间窗: Day 1 and Day 14
Simvastatin (Reference) ESL + Simvastatin (Test)
Simvastatin Cmax (Maximum Plasma Concentration)
时间窗: Day 1 and Day 14
Simvastatin (Reference) ESL + Simvastatin (Test)
Simvastatin AUC0-∞ (AUC From Time Zero to Infinity)
时间窗: Day 1 and Day 14
Simvastatin (Reference) ESL + Simvastatin (Test)
次要结局
未报告次要终点