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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Adult Male and Female Volunteers
• Intervention / Treatment: Drug: EYP651/Vonafexor low dose; Drug: EYP651/Vonafexor high dose; Drug: EYP651/CYP3A4 inhibitor; Drug: EYP651/Transporter substrate; Drug: EYP651/CYP2C8 and CYP2C9 substrate

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Project Manager; Phone Number: +33 (0)4 37 70 02 19; Email: mod@enyopharma.com

Study Locations

• France
  • Gières, France
    • Recruiting
    • Eurofins Optimed
    • Contact: Clinical Project Manager; Phone Number: +33 (0)4 37 70 02 19; Email: mod@enyopharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vonafexor low dose; Vonafexor low dose 1 tablet per day	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
Experimental: Vonafexor high dose; Vonafexor high dose 1 tablet per day	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
Experimental: EYP651 low dose; EYP651 low dose 1 tablet per day	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
Experimental: EYP651 high dose; Vonafexor high dose 1 tablet per day	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
Active Comparator: CYP3A4 inhibitor; Oral daily administration	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
Active Comparator: Transporter substrate; Oral daily administration	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
Active Comparator: CYP2C8 and CYP2C9 substrate; Oral daily administration	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Enyo Pharma

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2025
• Primary Completion (Actual): December 18, 2025
• Study Completion (Estimated): October 28, 2026

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetic; Pharmacodynamic; Drug-Drug Interactions
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Amino Acids, Peptides, and Proteins; Proteins; Pharmacologic Actions; Chemical Actions and Uses; Enzymes; Enzymes and Coenzymes; Oxidoreductases; Cytochromes; Mixed Function Oxygenases; Oxygenases; Hemeproteins; Metabolic Side Effects of Drugs and Substances; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 2; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 CYP2C8
• Other Study ID Numbers: EYP001-110; 2025-522915-40-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underline published results might be shared upon request with researchers who provide a methodologically sound proposal and to achieve objectives as set in the approved proposal.
• IPD Sharing Time Frame: PD will be shared deidentified and from 3 months and ending 5 years following article publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No