Phase I, Open-label Drug Interaction Study Between Eslicarbazepine Acetate 1200mg and Phenytoin 300 mg Following Multiple Dose Administrations in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 主要终点
- Cmax - the Maximum Plasma Concentration
研究概览
简要总结
Single centre, open-label, multiple doses, two parallel study groups each receiving two formulations in a one-sequence design
详细描述
Single centre, open-label, multiple doses, two parallel study groups each receiving two formulations in a one-sequence design:
Group A: Pre-treatment with ESL, treatment with ESL and ascending doses of phenytoin (PHT) in last phases;
Group B: Pre-treatment with PHT, treatment with PHT and ascending doses of ESL in last phases
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Availability of volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer
- •Non-black male aged of at least 18 years but not older than 45 years with a body mass index (BMI) greater than or equal to 19 and below 30 kg/m2
- •Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance (laboratory tests are presented in section 6.1.1.3)
- •Healthy according to the medical history, laboratory results and physical examination
- •Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day, and an ex-smoker is defined as someone who completely stopped smoking for at least 12 months before day 1 of this study
排除标准
- •Significant history of hypersensitivity to phenytoin, eslicarbazepine, oxcarbazepine, carbamazepine or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
- •Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
- •History of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability, including but not limited to cholecystectomy
- •Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease
- •Presence of significant heart disease or disorder according to ECG
- •Presence or history of significant central nervous system disorder like convulsion or depression
- •Hemoglobin count below 135 g/L (at screening)
- •Use of valproic acid in the previous 7 days prior to Day 1 of the study.
- •Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
- •Any clinically significant illness in the previous 28 days before day 1 of this study
- •Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids,phenytoin and rifampin), in the previous 28 days before Day 1 of this study.
研究组 & 干预措施
Group A BIA 2-093 + Phenytoin (PHT)
Day 1 to 2: Pre-treatment 1: 600 mg ESL Day 3 to 8: Treatment 1: 1200 mg ESL Day 9 to 10: Treatment 1 + Pre-treatment 2: 1200 mg ESL+ 100 mg PHT Day 11 to 27: Treatment 1 + Treatment 2: 1200 mg ESL + 300 mg PHT
干预措施: BIA 2-093 (Drug)
Group A BIA 2-093 + Phenytoin (PHT)
Day 1 to 2: Pre-treatment 1: 600 mg ESL Day 3 to 8: Treatment 1: 1200 mg ESL Day 9 to 10: Treatment 1 + Pre-treatment 2: 1200 mg ESL+ 100 mg PHT Day 11 to 27: Treatment 1 + Treatment 2: 1200 mg ESL + 300 mg PHT
干预措施: Phenytoin (Drug)
Group B BIA 2-093 + Phenytoin (PHT)
Day 1 to 2: Pre-treatment 2: 100 mg PHT Day 3 to 8: Treatment 2: 300 mg PHT Day 9 to 10: Treatment 2 + Pre-treatment 1: 300 mg PHT + 600 mg ESL Day 11 to 27: Treatment 1 + Treatment 2: 1200 mg ESL + 300 mg PHT
干预措施: BIA 2-093 (Drug)
Group B BIA 2-093 + Phenytoin (PHT)
Day 1 to 2: Pre-treatment 2: 100 mg PHT Day 3 to 8: Treatment 2: 300 mg PHT Day 9 to 10: Treatment 2 + Pre-treatment 1: 300 mg PHT + 600 mg ESL Day 11 to 27: Treatment 1 + Treatment 2: 1200 mg ESL + 300 mg PHT
干预措施: Phenytoin (Drug)
结局指标
主要结局
Cmax - the Maximum Plasma Concentration
时间窗: Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration
BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate
次要结局
- AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time(Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration)
- Tmax - the Time of Occurrence of Cmax(Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration)