A Three-part Single-center, Phase 1 Study to Assess the Tolerability, Safety, Pharmacokinetics (Including Food Interaction), and Pharmacodynamics of Ascending Single and Multiple Doses of AC-084 in Healthy Subjects and to Investigate the Pharmacokinetics of a Single Dose of AC-084 in Healthy CYP2C9 Poor Metabolizers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events (AEs) (Part A)
研究概览
简要总结
The primary purpose of this first-in-man study is to investigate whether AC-084 is safe and well-tolerated when orally administered at single- and multiple-ascending dose to healthy adults
详细描述
The study is designed in three parts, A, B and C
Part A: single-center, double-blind, randomized, placebo-controlled, single ascending dose
Part B: single-center, double-blind, randomized, placebo-controlled, multiple ascending dose
Part C: single-center, open-label, single dose in CYP2C9 poor metabolizers
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent in the local language prior to any study-mandated procedure
- •Healthy male subjects for Part A, healthy male and female subjects for Part B and Part C aged between 18 and 55 years (inclusive) at screening
- •No clinically significant findings on physical examination at screening
- •Body mass index (BMI) of 18.0 to 28.0 kg/m2 (inclusive) at screening
- •CYP2C9 poor metabolizers (Part C)
排除标准
- •History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study treatment (appendectomy and herniotomy allowed, cholecystectomy not allowed)
- •Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
- •Treatment or substances known to induce CYP enzyme drug metabolism within 30 days prior to first study treatment administration
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
- •Known allergic reactions or hypersensitivity to the study treatment or drugs of the same class, or any of their excipients
- •For Part A and Part B, CYP2C9 poor metabolizers enrolled in a cohort to be dosed with single or multiple dose of 500 mg or higher of ACT-774312 (confirmed by genotyping before enrollment)
研究组 & 干预措施
AC-084, single ascending dose (Part A)
AC-084 administered at different single dose levels in a sequential manner, and in a maximum of 7 dose levels starting from 1 mg (number of cohorts and dose levels will depend on the safety and pharmacokinetic results of the previous cohort). Each dose level will be investigated in a new group of at least 8 healthy male subjects (6 on active drug and 2 on placebo)
干预措施: AC-084 (Drug)
Placebo,single ascending dose (Part A)
Matched placebo administered as single ascending doses in parallel to AC-084
干预措施: Placebo (Drug)
AC-084, multiple ascending dose (Part B)
AC-084 administered in a twice daily (b.i.d.) dosing regimen at multiple dose levels. The starting dose will be between 1 and 30 mg and will be selected on the basis of the safety and pharmacokinetic results of the part A. Each dose level will be investigated in a new group of at least 8 healthy male subjects (6 on active drug and 2 on placebo)
干预措施: AC-084 (Drug)
Placebo,multiple ascending dose (Part B)
Matched placebo administered as multiple ascending doses in parallel to AC-084
干预措施: Placebo (Drug)
AC-084, single dose (Part C)
Up to 6 subjects in part C will receive AC-084 administered at a single dose (foreseen to be 100 mg)
干预措施: AC-084 (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs) (Part A)
时间窗: From dosing until day 4
Treatment-emergent AEs and treatment-emergent serious AEs
Number of participants with adverse events (AEs) (Part B)
时间窗: From dosing until day 8
Treatment-emergent AEs and treatment-emergent serious AEs
Number of participants with adverse events (AEs) (Part C)
时间窗: From dosing until day 6
Treatment-emergent AEs and treatment-emergent serious AEs
Incidence of safety events of interest (Part A)
时间窗: From dosing until day 4
Events of interest are any abnormalities in ECG, vital signs or laboratory test results
Incidence of safety events of interest (Part B)
时间窗: From dosing until day 8
Events of interest are any abnormalities in ECG, vital signs or laboratory test results
Incidence of safety events of interest (Part C)
时间窗: From dosing until day 6
Events of interest are any abnormalities in ECG, vital signs or laboratory test results
次要结局
- Terminal half-life [t(1/2)] following single oral ascending doses (Part B)(From dosing until day 8)
- Time to reach Cmax (tmax) following single oral ascending doses (Part C)(From dosing until day 6)
- Terminal half-life [t(1/2)] following single oral ascending doses (Part A)(From dosing until day 4)
- Maximum plasma concentration (Cmax) following single oral ascending doses (Part A)(From dosing until day 4)
- Maximum plasma concentration (Cmax) following single oral ascending doses (Part B)(From dosing until day 8)
- Maximum plasma concentration (Cmax) following single oral ascending doses (Part C)(From dosing until day 6)
- Time to reach Cmax (tmax) following single oral ascending doses (Part A)(From dosing until day 4)
- Time to reach Cmax (tmax) following single oral ascending doses (Part B)(From dosing until day 8)
- Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part A)(From dosing until day 4)
- Terminal half-life [t(1/2)] following single oral ascending doses (Part C)(From dosing until day 6)
- Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part B)(From dosing until day 8)
- Area under the plasma concentration-time curve (AUC) following single oral ascending doses (Part C)(From dosing until day 6)