Clinical trial NCT05249348: Effect of Food on PC14586 in Healthy Volunteers and the PK of PC14586 in Healthy Japanese Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Y220C
PC14586
PMV Pharma
PMV
food effect
Pharmacokinetics
Japanese
Lead sponsor: PMV Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2022-02-21
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single-dose crossover study one dose with food and one dose without food.
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Effect of a high-fat meal on AUClast
timeFrame: 2 months
measure: Part 1: Effect of a high-fat meal on AUC0-inf
timeFrame: 2 months
measure: Part 1: Effect of a high-fat meal on the Tmax
timeFrame: 2 months
measure: Part 1: Effect of a high-fat meal on the Cmax
timeFrame: 2 months
measure: Part 2: Effect of a high-fat meal on the AUC0-last
timeFrame: 7 months
measure: Part 2: Effect of a high-fat meal on the AUC0-inf
timeFrame: 7 months
measure: Part 2: Effect of a high-fat meal on the Tmax
timeFrame: 7 months
measure: Part 2: Effect of a high-fat meal on the Cmax
timeFrame: 7 months
Secondary outcomes:
measure: Part 1: Treatment emergent adverse events (TEAE)
timeFrame: 5 months
measure: Part 1: Clinically relevant changes in: physical examinations, vital signs, clinical laboratory tests, 12-lead triplicate electrocardiogram (ECG)
timeFrame: 5 months
measure: Part 2: AUC0-last of PC14586
timeFrame: 6 months
measure: Part 2: AUC0-inf of PC14586
timeFrame: 6 months
measure: Part 2: Cmax of PC14586
timeFrame: 6 months
measure: Part 2: Tmax of PC14586
timeFrame: 6 months
measure: Part 2: The apparent clearance (CL/F) of PC14586
timeFrame: 6 months
measure: Part 2: Volume of distribution (Vz/F) of PC14586
timeFrame: 6 months
measure: Half-life of PC14586
timeFrame: 6 months
measure: Part 2: Incidence of Treatment emergent adverse events (TEAE)
timeFrame: 10 months
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Parexel Early Phase Clinical Unit - Los Angeles
state: California
Study officials:
References: