Single-center, Open-label, Phase 1 Study Consisting of a Single-dose Pilot Phase and a Randomized, Two-way Crossover, Single-dose Main Phase to Investigate the Absolute Bioavailability of a Single Oral Dose of Selexipag in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 主要终点
- Absolute bioavailability (F) of selexipag
研究概览
简要总结
The primary purpose of this phase 1 study is to investigate the absolute bio-availability of a single oral dose of selexipag, i.e., to assess the amount of selexipag which reaches the blood when administered as an oral tablet (ACT-293987) compared to an intravenous administration in healthy subjects.
详细描述
A pilot phase was conducted in 3 male subjects before the main phase for assessment of absolute bio-availability conducted in 16 other male subjects. The pilot phase aimed to determine the intravenous dose to be used in the main phase based on safety data and pharmacokinetics data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 prior to any study-mandated procedure
- •Aged from 18 to 45 (inclusive) at screening
- •Body mass index (BMI) from 18.0 to 28.0 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 drug formulations
- •History or presence of any disease or 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 drugs
- •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
Intravenous selexipag (Pilot phase)
Subjects received a 20-minute intravenous (i.v.) infusion of 50 µg selexipag
干预措施: Selexipag for intravenous use (Drug)
Sequence A-B (Main phase)
Subjects received a 80-minute i.v. infusion of 200 µg selexipag during Period 1, and 2 tablets of oral selexipag (total dose of 400 µg) as a single administration during Period 2. A washout period of 7 to 10 days separated the i.v. infusion from the oral administration.
干预措施: Selexipag for intravenous use (Drug)
Sequence A-B (Main phase)
Subjects received a 80-minute i.v. infusion of 200 µg selexipag during Period 1, and 2 tablets of oral selexipag (total dose of 400 µg) as a single administration during Period 2. A washout period of 7 to 10 days separated the i.v. infusion from the oral administration.
干预措施: Selexipag for oral use (Drug)
Sequence B-A (Main phase)
Subjects received 2 tablets of oral selexipag (total dose of 400 µg) as a single administration during Period 1, and a 80-minute i.v. infusion of 200 µg selexipag during Period 2. A washout period of 7 to 10 days separated the oral administration from the i.v. infusion.
干预措施: Selexipag for intravenous use (Drug)
Sequence B-A (Main phase)
Subjects received 2 tablets of oral selexipag (total dose of 400 µg) as a single administration during Period 1, and a 80-minute i.v. infusion of 200 µg selexipag during Period 2. A washout period of 7 to 10 days separated the oral administration from the i.v. infusion.
干预措施: Selexipag for oral use (Drug)
结局指标
主要结局
Absolute bioavailability (F) of selexipag
时间窗: From pre-dose to 72 hours post-dose
F was calculated using the areas under the plasma concentrations curves extrapolated to infinity \[AUC(0-inf)\] after oral (po) and intravenous (iv) doses, obtained during the main phase, and using the following formula: AUC(0-inf)po \* iv dose / AUC(0-inf)iv \* oral dose
Area under the plasma concentration-time curve from time 0 to infinity [AUC(0-inf)] of selexipag
时间窗: From pre-dose to 72 hours post-dose
AUC(0-inf) was calculated from the concentration-time profile of selexipag after both oral and intravenous administration during the main phase
次要结局
- time to reach maximum plasma concentration (tmax) of selexipag and its active metabolite(From pre-dose to 72 hours post-dose)
- Maximum plasma concentration (Cmax) of selexipag and its active metabolite(From pre-dose to 72 hours post-dose)
- Areas under the plasma concentration-time curve from time 0 to time t [AUC(0-t)] of selexipag and its active metabolite(From pre-dose to 72 hours post-dose)
- Terminal half-life [t(1/2)] of selexipag and its active metabolite(From pre-dose to 72 hours post-dose)
- Number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)(4 days)