Healthy Adult Male and Female Volunteers
Conditions
Keywords
Drug-Drug Interactions, Pharmacokinetic, Pharmacodynamic
Brief summary
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.
Detailed description
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.
Interventions
DRUGEYP651/Vonafexor low dose
Repeated daily dosing with EYP651 or Vonafexor Acid for 5 days, cross-over at low dose according to period 1
DRUGEYP651/Vonafexor high dose
Repeated daily dosing with EYP651 or Vonafexor Acid for 5 days, cross-over at high dose according to period 1
DRUGEYP651/CYP3A4 inhibitor
Repeated daily dosing with EYP651 alone in period 1, and combined administration repeated daily dosing of EYP651 with index drug 1 (CYP3A4 inhibitor) in period 3. Parallel group 1
DRUGEYP651/Transporter substrate
Repeated daily dosing with EYP651 alone in period 1, and combined administration repeated daily dosing of EYP651 with index drug 2 (Transporter substrate) in period 3. Parallel group 2
DRUGEYP651/CYP2C8 and CYP2C9 substrate
Repeated daily dosing with EYP651 alone in period 1, Repeated daily dosing with the index drug 3 alone in period 2 and combined administration repeated daily dosing of EYP651 with index drug 3 (CYP2C8 and CYP2C9 substrate) in period 3. Parallel group 3
Sponsors
Enyo Pharma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Crossover study model for the part A of the study. Parallel study model for the part B of the study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Pharmacokinetic Area Under the Curve (AUC) | 1 day | Compare the single dose PK AUC of EYP651 and Vonafexor |
| Part A: Pharmacokinetic Maximum Plasma Concentration (Cmax) | 1 day | Compare the single dose PK Cmax of EYP651 and Vonafexor |
| Part A: Pharmacokinetic AUC | 5 days | Compare the multiple dose PK AUC of EYP651 and Vonafexor |
| Part A: Pharmacokinetic Cmax | 5 days | Compare the multiple dose PK Cmax of EYP651 and Vonafexor |
| Part B: CYP3A4 inhibition change in AUC | 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 | 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 | 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 | 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 | 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 | 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 |
Countries
France
Contacts
CONTACTClinical project manager
Outcome results
None listed