Single Dose ADME Study of [14C]-Rencofilstat in Healthy Male Subjects

An Open Label, Single-Dose, Single-Period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-Rencofilstat in Healthy Male Subjects

This is a single-center, single-period, single-dose, open-label, non-randomized study to assess the mass balance recovery, metabolite profile and metabolite identification of 14C- labelled rencofilstat ([14C] CRV431). It is planned to enroll 6 healthy male subjects in a single group. Each subject will receive a single 225 mg oral dose of [14C] CRV431 self-micro emulsifying drug delivery system (SMEDDS) oral emulsion.

Study Overview

• Status: Active, not recruiting
• Conditions: NASH With Fibrosis
• Intervention / Treatment: Drug: [14C]-rencofilstat 225mg

Detailed Description

This is a single center, open-label, non-randomized, single period, single dose study in healthy male subjects designed to assess the mass balance recovery, pharmacokinetics (PK), metabolite profile and metabolite identification of rencofilstat. It is planned to enroll a single cohort of 6 subjects. All subjects will receive a single 225 mg oral dose of [14C]-rencofilstat, as a SMEDDS oral emulsion in the fasted state.

Subjects will undergo preliminary screening procedures for the study at the screening visit (Day -28 to Day -2). Subjects will be admitted in the evening on the day before dosing (Day-1).

Whole blood, plasma, urine and feces samples will be collected at regular intervals for PK analysis, total radioactivity analysis, metabolite profiling, mass balance and safety as applicable, from pre-dose to discharge from the clinical unit. Urine and feces samples may be collected at return visits or home visits if mass balance criteria have not been met by a subject.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jill Greytok; Phone Number: 732-902-4016; Email: jgreytok@hepionpharma.com

Study Locations

• United Kingdom
  • Nottingham, United Kingdom
    • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy males
2. Aged 30 to 65 years inclusive at the time of signing informed consent
3. Body mass index (BMI) of 18.0 to 35.0 kg/m2 as measured at screening
4. Must be willing and able to communicate and participate in the whole study
5. Must have regular bowel movements (ie average stool production of ≥1 and ≤3 stools per day)
6. Must provide written informed consent
7. Must agree to adhere to the contraception requirements

Exclusion Criteria:

1. Subjects who have received any investigational treatment in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer
2. Subjects who are, or are immediate family members of, a study site or sponsor employee
3. Evidence or history of current SARS-CoV-2 infection within 4 weeks prior to study drug administration
4. History of any drug or alcohol abuse in the past 2 years prior to screening
5. Regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type)
6. A confirmed positive alcohol breath test at screening or admission
7. Current smokers and those who have smoked within the last 12 months prior to screening
8. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission
9. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months prior to screening
10. Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study
11. Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screening
12. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects known to have Gilbert's syndrome are excluded
13. Confirmed positive drugs of abuse test result
14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results
15. Evidence of renal impairment at screening, as indicated by an estimated eGFR of <60 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration equation
16. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, malabsorptive, neurological or psychiatric disorder, as judged by the investigator
17. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
18. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
19. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood
20. Subjects who have taken known strong or moderate CYP3A4 inducers in the 30 days before IMP administration
21. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day) in the 14 days before study drug administration. Exceptions may apply, as determined by the investigator, if each of the following criteria are met: medication with a short half-life if the washout is such that no pharmacodynamic activity is expected by the time of dosing with study drug; and if the use of medication does not jeopardize the safety of the trial subject; and if the use of medication is not considered to interfere with the objectives of the study
22. Subjects who have had a COVID-19 vaccine 7 days before dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [14C]-RCF 225mg; [14C]-rencofilstat, 225mg oral dose, self-micro-emulsifying drug delivery system, single dose	Drug: [14C]-rencofilstat 225mg; radio-labelled 225mg oral dose of rencofilstat; Other Names: CRV431

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the mass balance recovery after a single oral dose of [14C]-rencofilstat	Cumulative amount of total radioactivity recovered.	22 Days

Collaborators and Investigators

• Sponsor: Hepion Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Litza McKenzie, MD, Quotient Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: February 10, 2023
• First Submitted That Met QC Criteria: February 10, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Nonalcoholic Steatohepatitis; NAFLD; NASH
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis
• Other Study ID Numbers: HEPA-CRV431-105

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No