AME Study of [14C]-PC14586 in Healthy Male Participants

A Phase 1, Open-label Study of the Absorption, Metabolism, Excretion of [14C]-PC14586 Following a Single Oral Dose in Healthy Male Participants

This study will assess the PK and rates of elimination and mass balance of total radioactivity from [14C]-PC14586

PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation. The study will assess the PK, absorption, metabolism, and excretion of [14C]-PC14586 following a single dose in healthy male participants.

The aim is to recruit approximately 8 participants with a minimum number of 6 evaluable participants.

Each participant will be admitted to the study site pre-dose on Day -1 and will remain at the study site until at least Day 14. Participants will receive a single administration of [14C]-PC14586 as oral capsules on Day 1. During this study, whole blood, plasma, urine, feces, and vomit samples (if presented) will be collected at various timepoints to characterize the absorption, metabolism, excretion, and PK of [14C]-PC14586.

The duration of the residential period will be evaluated following the administration of [14C]-PC14586 and may be extended to ensure recovery of at least 90% of the total radioactivity, or until less than 1% of dose is recovered in urine and/or feces.

Inclusion Criteria:

1. Healthy, non-smoking males of any race, between 18 and 55 years of age, with BMI between 18.0 and 32.0 kg/m2 inclusive.
2. In good health, determined by no clinically significant findings from medical history and evaluations at screening and check-in as assessed by the investigator.
3. Agree to use a highly effective method of contraception from check-in through 90 days after discharge.
4. History of a minimum of 1 bowel movement per day.
5. Creatinine clearance ≥90 mL/min determined using the Cockcroft-Gault equation.
6. Able to swallow capsules.

Exclusion Criteria:

1. Significant history or clinical manifestation of any medical condition, disease or disorder, as determined by the investigator.
2. Blood pressure >140 mm systolic or >90 diastolic at screening or Day -1.
3. Positive hepatitis panel and/or positive human immunodeficiency virus test
4. Use or intend to use any prescription and/or nonprescription medications/products within14 days prior to check-in.
5. Participation in a clinical study involving last administration of an investigational drug within the past 30 days prior to dosing, or within 5 half-lives of the IMP, whichever is longer, or who have participated in more than 3 radiolabeled drug studies in the last 12 months.
6. Participants who have previously completed or withdrawn from this study or any other study investigating PC14586, or have previously received PC14586.
7. Participants with a history of alcoholism or drug/chemical abuse within 2 years prior to check-in, use of tobacco or nicotine-containing products within 3 months prior to check-in or with a positive drug and/or alcohol test result at check-in.
8. A positive p53 Y220C germline test at screening