A Phase 1, Two Parts, Open-label, Pharmacokinetic Comparison of Vonafexor Acid and Its Lysine Salt (EYP651) in Healthy Volunteers and Evaluation of Potential Drug-Drug Interactions
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Enyo Pharma
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Part A: Pharmacokinetic AUC
研究概览
简要总结
The purpose of this study is to define and compare the pharmacokinetic (PK) and pharmacodynamic (PD) profile of EYP651 at two dose levels and compare it with Vonafexor Acid PK and PD profile, the Part A.
In addition, Part B of the trial will assess the Drug-Drug Interactions (DDI) potential with the high dose of EYP651.
详细描述
The two parts are open-label and randomized, with a 2 periods, cross-over design for part A and a 3-period-parallel-arm design for Part B.
Expected duration for part A is approximately 8 weeks and Part B is approximately 12 weeks for each participating subject.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subject, aged 18-65 years inclusive.
- •Females of childbearing potential: commitment to use a highly effective method of birth control which result in a low failure rate.
- •Females of non-childbearing potential: either at least 3 months surgically sterilized or at least 1-year postmenopausal confirmed by the follicle stimulating hormone (FSH) level.
- •Males: commitment to use an adequate contraceptive method consistently and correctly.
- •Negative pregnancy test for childbearing potential women or FSH ≥ 40 IU/mL for postmenopausal women.
- •Non-smoker subject or smoker of maximum 5 cigarettes a day and able to stop during the study.
- •Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive.
- •Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination).
- •Normal Blood Pressure and Heart Rate.
- •Normal ECG recording on a 12-lead ECG.
- •Laboratory parameters within the normal range of the laboratory (hematology, hemostasis, blood chemistry tests, urinalysis).
- •Normal dietary habits.
- •Signing a written informed consent prior to selection.
- •Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.
排除标准
- •Any relevant history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic or infectious disease.
- •Frequent headaches and / or migraine, recurrent nausea and / or vomiting.
- •Symptomatic hypotension whatever the decrease of blood pressure or asymptomatic postural hypotension.
- •Blood donation in the 2 months before administration.
- •General anaesthesia in the 3 months before administration.
- •Presence or history of drug allergic condition and/or hypersensitivity.
- •Inability to abstain from intense muscular effort.
- •Any drug intake (except paracetamol and contraceptives) during the month prior to the first administration.
- •History or presence of drug or alcohol abuse (alcohol consumption > 40 grams / day).
- •Excessive consumption of beverages with xanthine bases (> 4 cups or glasses / day).
- •Positive Hepatitis B surface antigen or anti Hepatitis C Virus antibody, or positive results for Human Immunodeficiency Virus 1 or 2 tests.
- •Positive results for drugs of abuse tests.
- •No possibility of contact subject in case of emergency.
- •Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development.
- •Exclusion period of a previous study.
- •Administrative or legal supervision.
- •Subject who would receive more than 6'000 euros as indemnities for his participation in biomedical research within the 12 last months, including the indemnities for the present study.
研究组 & 干预措施
Vonafexor low dose
Vonafexor low dose 1 tablet per day
干预措施: EYP651/Vonafexor low dose (Drug)
Vonafexor high dose
Vonafexor high dose 1 tablet per day
干预措施: EYP651/Vonafexor high dose (Drug)
EYP651 low dose
EYP651 low dose 1 tablet per day
干预措施: EYP651/Vonafexor low dose (Drug)
EYP651 high dose
Vonafexor high dose 1 tablet per day
干预措施: EYP651/Vonafexor high dose (Drug)
EYP651 high dose
Vonafexor high dose 1 tablet per day
干预措施: EYP651/CYP3A4 inhibitor (Drug)
EYP651 high dose
Vonafexor high dose 1 tablet per day
干预措施: EYP651/Transporter substrate (Drug)
EYP651 high dose
Vonafexor high dose 1 tablet per day
干预措施: EYP651/CYP2C8 and CYP2C9 substrate (Drug)
CYP3A4 inhibitor
Oral daily administration
干预措施: EYP651/CYP3A4 inhibitor (Drug)
Transporter substrate
Oral daily administration
干预措施: EYP651/Transporter substrate (Drug)
CYP2C8 and CYP2C9 substrate
Oral daily administration
干预措施: EYP651/CYP2C8 and CYP2C9 substrate (Drug)
结局指标
主要结局
Part A: Pharmacokinetic AUC
时间窗: 5 days
Compare the multiple dose PK AUC of EYP651 and Vonafexor
Part A: Pharmacokinetic Area Under the Curve (AUC)
时间窗: 1 day
Compare the single dose PK AUC of EYP651 and Vonafexor
Part A: Pharmacokinetic Maximum Plasma Concentration (Cmax)
时间窗: 1 day
Compare the single dose PK Cmax of EYP651 and Vonafexor
Part A: Pharmacokinetic Cmax
时间窗: 5 days
Compare the multiple dose PK Cmax of EYP651 and Vonafexor
Part B: CYP3A4 inhibition change in AUC
时间窗: 5 days
To assess the effect of strong CYP3A4 inhibition on the pharmacokinetic AUC of EYP651 using Index drug 1, to evaluate EYP651 as an object of CYP3A4 inhibition
Part B: CYP3A4 inhibition change in Cmax
时间窗: 5 days
To assess the effect of strong CYP3A4 inhibition on the pharmacokinetic Cmax of EYP651 using Index drug 1, to evaluate EYP651 as an object of CYP3A4 inhibition
Part B: Transporter sensitive substrate change in AUC
时间窗: 5 days
To characterize the effect of EYP651 on the pharmacokinetic AUC of transporter sensitive substrate (Index drug 2) with EYP651 as the precipitant
Part B: Transporter sensitive substrate change in Cmax
时间窗: 5 days
To characterize the effect of EYP651 on the pharmacokinetic Cmax of transporter sensitive substrate (Index drug 2) with EYP651 as the precipitant
Part B: CYP2C8/CYP2C9 sensitive substrate change in AUC
时间窗: 5 days
To characterize the effect of EYP651 on the pharmacokinetic AUC of CYP2C8/CYP2C9 sensitive substrate (Index drug 3) with EYP651 as the precipitant
Part B: CYP2C8/CYP2C9 sensitive substrate change in Cmax
时间窗: 5 days
To characterize the effect of EYP651 on the pharmacokinetic Cmax of CYP2C8/CYP2C9 sensitive substrate (Index drug 3) with EYP651 as the precipitant
次要结局
未报告次要终点