Clinical trial NCT05523687: AME Study of [14C]-PC14586 in Healthy Male Participants
Official title: A Phase 1, Open-label Study of the Absorption, Metabolism, Excretion of [14C]-PC14586 Following a Single Oral Dose in Healthy Male Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Male Volunteers
Keywords: Y220C
PC14586
PMV Pharma
PMV
AME
Lead sponsor: PMV Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2022-08-31
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Characterize Maximum Plasma Concentration (Cmax) of PC14586 and PC14586 metabolite M1 (PC16163).
timeFrame: 1 month
measure: Characterize Time to Maximum Plasma Concentration (tmax) of PC14586 and PC14586 metabolite M1 (PC16163).
timeFrame: 1 month
measure: Characterize Total Drug Exposure (AUC0-inf) of PC14586 and PC14586 metabolite M1 (PC16163).
timeFrame: 1 month
measure: Characterize Total Drug Exposure to the last measurable concentration (AUC0-t) of PC14586 and PC14586 metabolite M1 (PC16163).
timeFrame: 1 month
measure: Characterize the Half-Life (t 1/2) of PC14586 and PC14586 metabolite M1 (PC16163).
timeFrame: 1 month
measure: Characterize the Clearance (CL/F) of PC14586 and PC14586 metabolite M1 (PC16163) after oral administration.
timeFrame: 1 month
measure: Characterize the Volume of Distribution (Vd/F) of PC14586 and PC14586 metabolite M1 (PC16163) after oral administration.
timeFrame: 1 month
measure: Determine the total radioactivity in whole blood and plasma of PC14586 and PC14586 metabolite M1 (PC16163).
timeFrame: 1 month
measure: Characterize total radioactivity (Xlast, feces) of PC14586 excreted in feces.
timeFrame: 1 month
measure: Characterize the half life of total radioactivity (Xt1-t2, feces) of PC14586 excreted in feces.
timeFrame: 1 month
measure: Characterize the fraction excreted of total radioactivity (fe last, feces) of PC14586 in feces.
timeFrame: 1 month
measure: Characterize the half-life of fraction excreted of total radioactivity (fe t1-t2, feces) of PC14586 in feces.
timeFrame: 1 month
measure: Characterize total radioactivity (Xlast, urine) of PC14586 excreted in urine.
timeFrame: 1 month
measure: Characterize the half life of total radioactivity (Xt1-t2, urine) of PC14586 excreted in urine.
timeFrame: 1 month
measure: Characterize the fraction excreted of total radioactivity (fe last, urine) of PC14586 in urine.
timeFrame: 1 month
measure: Characterize the half-life of fraction excreted of total radioactivity (fe t1-t2, urine) of PC14586 in urine.
timeFrame: 1 month
measure: Characterize the renal clearance (CLr) of PC14586 in urine.
timeFrame: 1 month
Secondary outcomes:
measure: Identification of PC14586 metabolite profiles in plasma, urine and feces.
timeFrame: 1 month
measure: Identification of the incidence and severity of adverse events after administration of PC14586.
timeFrame: 1 month
measure: Identification of the incidence of laboratory abnormalities based on hematology, clinical chemistry and urine test results of PC14586.
timeFrame: 1 month
measure: Identification of 12-lead electrocardiogram (ECG) abnormalities after a single dose of PC14586.
timeFrame: 1 month
measure: Identification of abnormal blood pressure after a single dose of PC14586.
timeFrame: 1 month
measure: Identification of abnormal pulse rate after a single dose of PC14586.
timeFrame: 1 month
measure: Identification of abnormal oral body temperature after a single dose of PC14586.
timeFrame: 1 month
Other outcomes:
Locations:
city: Madison
country: United States
facility: Labcorp Clinical Research Unit Inc.
state: Wisconsin
Study officials:
References: