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

Study Overview

• Status: Completed
• Conditions: Healthy Male Volunteers
• Intervention / Treatment: Drug: [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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Labcorp Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Single, oral dose of [14C]-PC14586; Healthy, male participants will receive a single, oral dose of [14C]-PC14586	Drug: [14C]-PC14586; Single, oral dose of [14C]-PC14586

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize Maximum Plasma Concentration (Cmax) of PC14586 and PC14586 metabolite M1 (PC16163).	Determine Cmax for PC14586 and PC16163 in plasma.	1 month
Characterize Time to Maximum Plasma Concentration (tmax) of PC14586 and PC14586 metabolite M1 (PC16163).	Determine tmax for PC14586 and PC16163 in plasma.	1 month
Characterize Total Drug Exposure (AUC0-inf) of PC14586 and PC14586 metabolite M1 (PC16163).	Determine AUC0-inf for PC14586 and PC16163 in plasma.	1 month
Characterize Total Drug Exposure to the last measurable concentration (AUC0-t) of PC14586 and PC14586 metabolite M1 (PC16163).	Determine AUC0-t for PC14586 and PC16163 in plasma.	1 month
Characterize the Half-Life (t 1/2) of PC14586 and PC14586 metabolite M1 (PC16163).	Determine t 1/2 for PC14586 and PC16163 in plasma.	1 month
Characterize the Clearance (CL/F) of PC14586 and PC14586 metabolite M1 (PC16163) after oral administration.	Determine CL/F for PC14586 and PC16163 in plasma.	1 month
Characterize the Volume of Distribution (Vd/F) of PC14586 and PC14586 metabolite M1 (PC16163) after oral administration.	Determine Vd/F for PC14586 and PC16163 in plasma.	1 month
Determine the total radioactivity in whole blood and plasma of PC14586 and PC14586 metabolite M1 (PC16163).	Determine total radioactivity for PC14586 and PC16163 in whole blood and plasma.	1 month
Characterize total radioactivity (Xlast, feces) of PC14586 excreted in feces.	Determine total radioactivity of PC14586 excreted in feces	1 month
Characterize the half life of total radioactivity (Xt1-t2, feces) of PC14586 excreted in feces.	Determine half life of total radioactivity of PC14586 excreted in feces.	1 month
Characterize the fraction excreted of total radioactivity (fe last, feces) of PC14586 in feces.	Determine the fraction excreted of total radioactivity of PC14586 in feces.	1 month
Characterize the half-life of fraction excreted of total radioactivity (fe t1-t2, feces) of PC14586 in feces.	Determine half-life of fraction excreted of total radioactivity of PC14586 in feces.	1 month
Characterize total radioactivity (Xlast, urine) of PC14586 excreted in urine.	Determine total radioactivity of PC14586 excreted in urine.	1 month
Characterize the half life of total radioactivity (Xt1-t2, urine) of PC14586 excreted in urine.	Determine half life of total radioactivity of PC14586 excreted in urine.	1 month
Characterize the fraction excreted of total radioactivity (fe last, urine) of PC14586 in urine.	Determine the fraction excreted of total radioactivity of PC14586 in urine.	1 month
Characterize the half-life of fraction excreted of total radioactivity (fe t1-t2, urine) of PC14586 in urine.	Determine half-life of fraction excreted of total radioactivity of PC14586 in urine.	1 month
Characterize the renal clearance (CLr) of PC14586 in urine.	Determine the renal clearance of PC14586 in urine.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of PC14586 metabolite profiles in plasma, urine and feces.	Identification of PC14586 metabolites in plasma (>10% relative total drug related exposure) and excreta (>10% of excreted dose).	1 month
Identification of the incidence and severity of adverse events after administration of PC14586.	Number of participants with adverse events.	1 month
Identification of the incidence of laboratory abnormalities based on hematology, clinical chemistry and urine test results of PC14586.	Number of participants with an incidence of laboratory abnormalities in test results.	1 month
Identification of 12-lead electrocardiogram (ECG) abnormalities after a single dose of PC14586.	Number of participants with abnormal 12-lead ECG results.	1 month
Identification of abnormal blood pressure after a single dose of PC14586.	Number of participants with abnormal blood pressure.	1 month
Identification of abnormal pulse rate after a single dose of PC14586.	Number of participants with abnormal pulse rate.	1 month
Identification of abnormal oral body temperature after a single dose of PC14586.	Number of participants with abnormal oral body temperature.	1 month

Collaborators and Investigators

• Sponsor: PMV Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2022
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: August 29, 2022
• First Posted (Actual): August 31, 2022

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: PC14586; Y220C; PMV; PMV Pharma; AME
• Other Study ID Numbers: PMV-586-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No