Single-center, Open-label, Randomized 2-way Crossover Study of the Effect of Lacosamide 200 mg Twice Daily on the Single-dose Pharmacokinetics and Pharmacodynamics of Warfarin (25 mg) in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- UCB Pharma
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Maximum prothrombin time (PTmax)
研究概览
简要总结
The purpose of this study is to investigate the effect of Lacosamide 200 mg twice a day (bid) on single dose pharmacokinetics (PK) and pharmacodynamics (PD) of Warfarin (25 mg) in healthy male volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male volunteers 18-55 years of age
- •BMI 18.0-30.0 kg/m2 and weight at least 50 kg
- •Tympanic body temperature 35.0-37.5°C (95 and 99.5°F) inclusive
排除标准
- •Volunteer has participated or is participating in any other clinical studies of investigational drug or another Investigational Medicinal Product (IMP) within the last 3 months
- •Volunteer is not healthy (eg, taking any drug treatments, excessive amount of alcohol, cigarettes or caffeine, having any medical or emotional/psychological problems, a drug/alcohol abuse, having abnormal safety parameters)
- •Volunteer is taking Warfarin or Non Steroidal Anti-Inflammatory Drug (NSAID)
- •Volunteer has history of suicide attempt
- •Volunteer has history of coagulation abnormalities, occult blood in stool, gastrointestinal ulcer, surgery within 6 months
结局指标
主要结局
Maximum prothrombin time (PTmax)
时间窗: Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period
Warfarin maximum international normalized ratio (INRmax)
时间窗: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period
Area under the Warfarin plasma concentration versus time curve from time 0 to the last quantifiable level, AUC0-t(Warfarin)
时间窗: Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period
Maximum Warfarin plasma concentration (Cmax)
时间窗: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period
Area under the Warfarin plasma concentration versus time curve from time 0 to infinity, AUC (Warfarin)
时间窗: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period
Warfarin area under the prothrombin time (PT) versus time curve (PTAUC)
时间窗: Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period
Warfarin area under the International Normalized Ratio (INR) versus time curve (INRAUC)
时间窗: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period
次要结局
- Lacosamide trough plasma concentration (Ctrough)(Morning pre dose sample on Days 3-10 or Days 24 -30 of Lacosamide BID dosing)
- Time of maximum Warfarin plasma concentration (Tmax)(Multiple sampling from 0 -168 hours following administration of a single Warfarin dose)
- CYP2C9 genotype(Single measurement on Day 1)
- VKORC1 genotype(Single measurement on Day 1)
- Change from Baseline in Systolic Blood Pressure at 24 h post dose(From pre dose to 24 h post dose Warfarin administration in each treatment period)
- Change from Baseline in Diastolic Blood Pressure at 24 h post dose(From pre dose to 24 h post dose Warfarin administration in each treatment period)
- Apparent volume of distribution of Warfarin (V /F)(Multiple sampling from 0 -168 hours following administration of a single Warfarin dose)
- First order terminal elimination rate constant of Warfarin(Multiple sampling from 0 -168 hours following administration of a single Warfarin dose)
- Change from Baseline in Systolic Blood Pressure at 4 h post dose(From pre dose to 4 h post dose LCM administration)
- Change from Baseline in Diastolic Blood Pressure at 12 h post dose(From pre dose to 12 h post dose LCM administration)
- Change from Baseline in Body Temperature at 12 h post dose(From pre dose to 12 h post dose LCM administration)
- Change from Baseline in Body Temperature at 24 h post dose(From pre dose to 24 h post dose Warfarin administration in each treatment period)
- Change from Baseline in Pulse Rate at 4 h post dose(From pre dose to 4 h post dose Lacosamide (LCM) administration)
- Occurrence of at Least One Treatment-emergent Adverse Event (TEAE) during the duration of the study(Duration of study is approximately 32 days)
- Change from Baseline in Pulse Rate at 12 h post dose(From pre dose to 12 h post dose LCM administration)
- Change from Baseline in Systolic Blood Pressure at 12 h post dose(From pre dose to 12 h post dose LCM administration)
- Change from Baseline in Body Temperature at 4 h post dose(From pre dose to 4 h post dose LCM administration)
- Terminal half-life of Warfarin (T ½)(Multiple sampling from 0 -168 hours following administration of a single Warfarin dose)
- Apparent total body clearance of Warfarin (CL /F)(Multiple sampling from 0 -168 hours following administration of a single Warfarin dose)
- Change from Baseline in Pulse Rate at 24 h post dose(From pre dose to 24 h post dose Warfarin administration in each treatment period)
- Change from Baseline in Diastolic Blood Pressure at 4 h post dose(From pre dose to 4 h post dose LCM administration)
- Change from Baseline in Body Temperature at 4h post dose(From pre dose to 4 h post dose Warfarin administration in each treatment period)