Single Dose ADME Study 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.

Inclusion Criteria:Healthy malesAged 30 to 65 years inclusive at the time of signing informed consentBody mass index (BMI) of 18.0 to 35.0 kg/m2 as measured at screeningMust be willing and able to communicate and participate in the whole studyMust have regular bowel movements (ie average stool production of ≥1 and ≤3 stools per day)Must provide written informed consentMust agree to adhere to the contraception requirementsExclusion 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 longerSubjects who are, or are immediate family members of, a study site or sponsor employeeEvidence or history of current SARS-CoV-2 infection within 4 weeks prior to study drug administrationHistory of any drug or alcohol abuse in the past 2 years prior to screeningRegular 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 admissionCurrent smokers and those who have smoked within the last 12 months prior to screeningA confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admissionCurrent users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months prior to screeningRadiation 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 studySubjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screeningClinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects known to have Gilbert's syndrome are excludedConfirmed positive drugs of abuse test resultPositive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody resultsEvidence of renal impairment at screening, as indicated by an estimated eGFR of <60 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration equationHistory of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, malabsorptive, neurological or psychiatric disorder, as judged by the investigatorSerious adverse reaction or serious hypersensitivity to any drug or the formulation excipientsPresence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is activeDonation of blood or plasma within the previous 3 months or loss of greater than 400 mL of bloodSubjects who have taken known strong or moderate CYP3A4 inducers in the 30 days before IMP administrationSubjects 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 studySubjects who have had a COVID-19 vaccine 7 days before dosing