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

Sponsor

PMV Pharmaceuticals, Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05249348

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: PC14586	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Single-dose crossover study one dose with food and one dose without food.Single-dose crossover study one dose with food and one dose without food.

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Dec 20, 2021

Anticipated Primary Completion Date :

Sep 20, 2022

Anticipated Study Completion Date :

Sep 20, 2022

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

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

Part 1: Treatment emergent adverse events (TEAE) [5 months]
Part 1: Clinically relevant changes in safety parameters: 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: Treatment emergent adverse events (TEAE) Clinically relevant changes in safety parameters: physical examinations, vital signs, clinical laboratory tests, 12-lead triplicate electrocardiogram (ECG) [10 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.