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

NCT07251153 | Recruiting Phase 1

• 2 other identifiers: EYP001-1102025-522915-40-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Adult Male and Female Volunteers

Keywords

Drug-Drug Interactions; Pharmacokinetic; Pharmacodynamic

Outcome Measures

Primary Outcomes (10)

• Part A: Pharmacokinetic Area Under the Curve (AUC)

  Compare the single dose PK AUC of EYP651 and Vonafexor

  1 day

• Part A: Pharmacokinetic Maximum Plasma Concentration (Cmax)

  Compare the single dose PK Cmax of EYP651 and Vonafexor

  1 day

• Part A: Pharmacokinetic AUC

  Compare the multiple dose PK AUC of EYP651 and Vonafexor

  5 days

• Part A: Pharmacokinetic Cmax

  Compare the multiple dose PK Cmax of EYP651 and Vonafexor

  5 days

• Part B: CYP3A4 inhibition change in AUC

  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

  5 days

• Part B: CYP3A4 inhibition change in Cmax

  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

  5 days

• Part B: Transporter sensitive substrate change in AUC

  To characterize the effect of EYP651 on the pharmacokinetic AUC of transporter sensitive substrate (Index drug 2) with EYP651 as the precipitant

  5 days

• Part B: Transporter sensitive substrate change in Cmax

  To characterize the effect of EYP651 on the pharmacokinetic Cmax of transporter sensitive substrate (Index drug 2) with EYP651 as the precipitant

  5 days

• Part B: CYP2C8/CYP2C9 sensitive substrate change in AUC

  To characterize the effect of EYP651 on the pharmacokinetic AUC of CYP2C8/CYP2C9 sensitive substrate (Index drug 3) with EYP651 as the precipitant

  5 days

• Part B: CYP2C8/CYP2C9 sensitive substrate change in Cmax

  To characterize the effect of EYP651 on the pharmacokinetic Cmax of CYP2C8/CYP2C9 sensitive substrate (Index drug 3) with EYP651 as the precipitant

  5 days

Study Arms (7)

Vonafexor low dose

EXPERIMENTAL

Vonafexor low dose 1 tablet per day

Drug: EYP651/Vonafexor low dose

Vonafexor high dose

EXPERIMENTAL

Vonafexor high dose 1 tablet per day

Drug: EYP651/Vonafexor high dose

EYP651 low dose

EXPERIMENTAL

EYP651 low dose 1 tablet per day

Drug: EYP651/Vonafexor low dose

EYP651 high dose

EXPERIMENTAL

Vonafexor high dose 1 tablet per day

Drug: EYP651/Vonafexor high dose; Drug: EYP651/CYP3A4 inhibitor; Drug: EYP651/Transporter substrate; Drug: EYP651/CYP2C8 and CYP2C9 substrate

CYP3A4 inhibitor

ACTIVE COMPARATOR

Oral daily administration

Drug: EYP651/CYP3A4 inhibitor

Transporter substrate

ACTIVE COMPARATOR

Oral daily administration

Drug: EYP651/Transporter substrate

CYP2C8 and CYP2C9 substrate

ACTIVE COMPARATOR

Oral daily administration

Drug: EYP651/CYP2C8 and CYP2C9 substrate

Interventions

EYP651/Vonafexor low dose DRUG

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

EYP651 low dose; Vonafexor low dose

EYP651/Vonafexor high dose DRUG

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

EYP651 high dose; Vonafexor high dose

EYP651/CYP3A4 inhibitor DRUG

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

CYP3A4 inhibitor; EYP651 high dose

EYP651/Transporter substrate DRUG

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

EYP651 high dose; Transporter substrate

EYP651/CYP2C8 and CYP2C9 substrate DRUG

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

CYP2C8 and CYP2C9 substrate; EYP651 high dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Administrative or legal supervision.

Sponsors & Collaborators

• Enyo Pharma: lead

Study Sites (1)

Eurofins Optimed

Gières, France

RECRUITING

MeSH Terms

Interventions

Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 CYP2C8

Intervention Hierarchy (Ancestors)

Cytochrome P-450 Enzyme Inhibitors; Metabolic Side Effects of Drugs and Substances; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 Enzyme System; Cytochromes; Enzymes and Coenzymes; Cytochrome P450 Family 2; Mixed Function Oxygenases; Oxygenases; Oxidoreductases; Enzymes; Hemeproteins; Proteins; Amino Acids, Peptides, and Proteins

Central Study Contacts

Clinical project manager

CONTACT

+33 (0)4 37 70 02 19; mod@enyopharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Crossover study model for the part A of the study. Parallel study model for the part B of the study

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 26, 2025
• Study Start: October 28, 2025
• Primary Completion: December 18, 2025
• Study Completion (Estimated): October 28, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: PD will be shared deidentified and from 3 months and ending 5 years following article publication.

Locations

FR (1)