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

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.

Inclusion criteria

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

Exclusion criteria

• 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
• Subjects who are, or are immediate family members of, a study site or sponsor employee
• Evidence or history of current SARS-CoV-2 infection within 4 weeks prior to study drug administration
• History of any drug or alcohol abuse in the past 2 years prior to screening
• 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)
• A confirmed positive alcohol breath test at screening or admission
• Current smokers and those who have smoked within the last 12 months prior to screening
• A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months prior to screening
• 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
• Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screening
• Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects known to have Gilbert's syndrome are excluded
• Confirmed positive drugs of abuse test result
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results
• 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
• History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, malabsorptive, neurological or psychiatric disorder, as judged by the investigator
• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
• Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood
• Subjects who have taken known strong or moderate CYP3A4 inducers in the 30 days before IMP administration
• 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
• Subjects who have had a COVID-19 vaccine 7 days before dosing