Pharmacokinetic Comparison of Vonafexor Acid and Its Lysine Salt and Evaluation of Potential Drug-Drug Interactions

Official title

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

Overview

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

• Drug EYP651/Vonafexor low dose
  Repeated daily dosing with EYP651 or Vonafexor Acid for 5 days, cross-over at low dose according to period 1
• Drug EYP651/Vonafexor high dose
  Repeated daily dosing with EYP651 or Vonafexor Acid for 5 days, cross-over at high dose according to period 1
• Drug EYP651/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
• Drug EYP651/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
• Drug EYP651/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

Primary outcome measures

• Part A: Pharmacokinetic Area Under the Curve (AUC) [Time frame: 1 day]
• Part A: Pharmacokinetic Maximum Plasma Concentration (Cmax) [Time frame: 1 day]
• Part A: Pharmacokinetic AUC [Time frame: 5 days]
• Part A: Pharmacokinetic Cmax [Time frame: 5 days]
• Part B: CYP3A4 inhibition change in AUC [Time frame: 5 days]
• Part B: CYP3A4 inhibition change in Cmax [Time frame: 5 days]
• Part B: Transporter sensitive substrate change in AUC [Time frame: 5 days]
• Part B: Transporter sensitive substrate change in Cmax [Time frame: 5 days]
• Part B: CYP2C8/CYP2C9 sensitive substrate change in AUC [Time frame: 5 days]
• Part B: CYP2C8/CYP2C9 sensitive substrate change in Cmax [Time frame: 5 days]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Eurofins Optimed — Gières

Identifiers

NCT: NCT07251153 · EYP001-110 · 2025-522915-40-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗