A Single-center, Open-label Study to Investigate the Food Effect on the Pharmacokinetics of ACT-541468 and the Effect of Single- and Multiple-dose ACT-541468 on the Pharmacokinetics of Midazolam and Its Metabolite 1-Hydroxymidazolam in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Terminal half-life (t1/2) of midazolam
研究概览
简要总结
The main objectives of this phase 1 trial are to evaluate the effect of food on the pharmacokinetics (i.e. how long and how much a compound is present in the blood) of ACT-541468 and to evaluate whether ACT-541468 can affect the pharmacokinetics of midazolam, a CYP3A4 substrate.
详细描述
Food effect will be assessed by comparing the pharmacokinetic (PK) parameters of a single dose of ACT-541468 under fasted (Treatment B) and fed (Treatment C) conditions.
Potential CYP3A4 inhibiting / inducing effects of ACT-541468 will be assessed by comparing the PK parameters of midazolam alone (Treatment A) and midazolam given with a single dose of ACT-541468 (Treatment B) or with multiple doses of ACT-541468 (Treatment D).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Signed informed consent form
- •Male subjects aged from 18 to 45 years (inclusive) at screening
- •Body mass index (BMI) from 18.0 to 30.0 kg/m2 (inclusive) at screening
- •Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests
排除标准
- •Any contraindication to the study treatments
- •History or clinical evidence of any disease or medical / surgical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study treatments
- •History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol
研究组 & 干预措施
Food effect and Drug-Drug interaction
Treatments will be given to all subjects in the same fixed sequence: Treatment A (Day 1, single dose of midazolam, fasted), Treatment B (Day 2, single dose of ACT-541468 followed by single dose of midazolam, fasted), Treatment C (Day 4, single dose ACT-541468, fed), Treatment D (multiple doses of ACT-541468 from Day 5 to Day 8 + single dose of midazolam on Day 8, fasted).
干预措施: Midazolam (Drug)
Food effect and Drug-Drug interaction
Treatments will be given to all subjects in the same fixed sequence: Treatment A (Day 1, single dose of midazolam, fasted), Treatment B (Day 2, single dose of ACT-541468 followed by single dose of midazolam, fasted), Treatment C (Day 4, single dose ACT-541468, fed), Treatment D (multiple doses of ACT-541468 from Day 5 to Day 8 + single dose of midazolam on Day 8, fasted).
干预措施: ACT-541468 (Drug)
结局指标
主要结局
Terminal half-life (t1/2) of midazolam
时间窗: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
t1/2 is calculated from the plasma concentrations-time curves of midazolam
Maximum plasma concentration (Cmax) of 1-hydroxymidazolam
时间窗: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Cmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam
Time to reach Cmax (tmax) of 1-hydroxymidazolam
时间窗: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Tmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam
Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam
时间窗: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
AUC is calculated from time zero to 24 hours post dose
Maximum plasma concentration (Cmax) of ACT-541468
时间窗: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
Cmax is directly determined from the plasma concentrations-time curves of ACT-541468
Time to reach Cmax (tmax) of ACT-541468
时间窗: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
Tmax is directly determined from the plasma concentrations-time curves of ACT-541468
Area under the plasma concentration-time curve [AUC(0-24)] of midazolam
时间窗: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
AUC is calculated from time zero to 24 hours post dose
Terminal half-life (t1/2) of 1-hydroxymidazolam
时间窗: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
t1/2 is calculated from the plasma concentrations-time curves of 1-hydroxymidazolam
Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468
时间窗: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
AUC is calculated from time zero to 24 hours post dose
Terminal half-life (t1/2) of ACT-541468
时间窗: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
t1/2 is calculated from the plasma concentrations-time curves of ACT-541468
Time to reach Cmax (tmax) of midazolam
时间窗: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Tmax is directly obtained from the plasma concentrations-time curves of midazolam
Maximum plasma concentration (Cmax) of midazolam
时间窗: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Cmax is directly obtained from the plasma concentrations-time curves of midazolam
次要结局
- Maximum plasma concentration (Cmax) of ACT-541468 metabolites(PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose)
- Time to reach Cmax (tmax) of ACT-541468 metabolites(PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose)
- Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 metabolites(PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose)
- Terminal half-life (t1/2) of ACT-541468 metabolites(PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose)
- Number of subjects with treatment-emergent adverse events and serious adverse events(From baseline to end-of-study, i.e.,maximum 5 days after Day 8)