Effect of Food on PC14586 in Healthy Volunteers and the PK of PC14586 in Healthy Japanese Volunteers

A Phase 1 Open-label, Cross-over Study to Assess the Effects of Food on PC14586 Pharmacokinetics in Healthy Volunteers and to Assess PC14586 Pharmacokinetics in Healthy Japanese Volunteers Living in the US

This is a 2-part Phase 1 cross-over study to assess the effects of food on the pharmacokinetics of PC14586 in healthy volunteers. The pharmacokinetics of PC14586 at a clinically relevant dose in Japanese participants will also be studied.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: PC14586

Detailed Description

PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the p53 Y220C mutation. This Phase 1 trial will be conducted in 2 parts (Part 1 - pilot and Part 2 - pivotal) to assess the pharmacokinetics of PC14586 in healthy volunteers including Japanese participants.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Parexel Early Phase Clinical Unit - Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy, non-smoking male and female Caucasian/ non-Asian or Japanese human volunteers
• 18 to 55 years of age
• Able to swallow tablets.

Inclusion criteria for Japanese participants only:

• Japanese and born in Japan (1st generation)
• The parents and grandparents of the participant are ethnically Japanese and born in Japan
• Has undergone no significant change in lifestyle since leaving Japan
• Has lived < 10 years outside of Japan

Exclusion Criteria:

• Clinically significant medical history as determined by the PI.
• Any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs.
• A p53 Y220C mutation.
• Blood pressure >140 mm systolic or >90 diastolic.
• Smoked or used other nicotine-containing products during the previous 3 months.
• History of alcohol and/or illicit drug abuse within the previous 5 years.
• Hepatitis B surface antigen (HBsAg), Hepatitis C antibody or human immunodeficiency virus (HIV).
• Positive blood test for ethanol.
• Positive urine drug test.
• Pregnancy or breastfeeding.
• Unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to admission until discharge from the clinical site.
• Has donated blood within 2 months prior to admission.
• Has used over-the-counter (OTC) medications (including vitamins), prescription medications or herbal remedies from 14 days prior to admission.
• Has used an investigational drug within 30 days prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Sequence A; Period 1 will be fed, then washout, then Period 2 will be fasted.	Drug: PC14586; An oral dose of PC14586 will be used in Arms A and B (Part 1) and a different dose will be used for Arms C and D and the Japanese cohort (Part 2).
Experimental: Part 1 Sequence B; Period 1 will be fasted, then washout, then Period 2 will be fed.	Drug: PC14586; An oral dose of PC14586 will be used in Arms A and B (Part 1) and a different dose will be used for Arms C and D and the Japanese cohort (Part 2).
Experimental: Part 2 Sequence C; Period 1 will be fed, then washout, then Period 2 will be fasted. A different dose of PC14586 will be tested.	Drug: PC14586; An oral dose of PC14586 will be used in Arms A and B (Part 1) and a different dose will be used for Arms C and D and the Japanese cohort (Part 2).
Experimental: Part 2 Sequence D; Period 1 will be fasted, then washout, then Period 2 will be fed. A different dose of PC14586 will be tested.	Drug: PC14586; An oral dose of PC14586 will be used in Arms A and B (Part 1) and a different dose will be used for Arms C and D and the Japanese cohort (Part 2).
Experimental: Part 2 Japanese Cohort; 6 Japanese participants will be administered a single dose of PC14586.	Drug: PC14586; An oral dose of PC14586 will be used in Arms A and B (Part 1) and a different dose will be used for Arms C and D and the Japanese cohort (Part 2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Effect of a high-fat meal on AUClast	2 months
Part 1: Effect of a high-fat meal on AUC0-inf	2 months
Part 1: Effect of a high-fat meal on the Tmax	2 months
Part 1: Effect of a high-fat meal on the Cmax	2 months
Part 2: Effect of a high-fat meal on the AUC0-last	7 months
Part 2: Effect of a high-fat meal on the AUC0-inf	7 months
Part 2: Effect of a high-fat meal on the Tmax	7 months
Part 2: Effect of a high-fat meal on the Cmax	7 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 1: Treatment emergent adverse events (TEAE)	5 months
Part 1: Clinically relevant changes in: physical examinations, vital signs, clinical laboratory tests, 12-lead triplicate electrocardiogram (ECG)	5 months
Part 2: AUC0-last of PC14586	6 months
Part 2: AUC0-inf of PC14586	6 months
Part 2: Cmax of PC14586	6 months
Part 2: Tmax of PC14586	6 months
Part 2: The apparent clearance (CL/F) of PC14586	6 months
Part 2: Volume of distribution (Vz/F) of PC14586	6 months
Half-life of PC14586	6 months
Part 2: Incidence of Treatment emergent adverse events (TEAE)	10 months

Collaborators and Investigators

• Sponsor: PMV Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2021
• Primary Completion (Actual): June 9, 2022
• Study Completion (Actual): June 9, 2022

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: February 9, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Japanese; food effect; PC14586; Y220C; PMV; PMV Pharma
• Other Study ID Numbers: PMV-586-102; 262612 (Other Identifier: Parexel)

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