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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: PC14586


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single-dose crossover study one dose with food and one dose without food.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Sequence A<br>Period 1 will be fed, then washout, then Period 2 will be fasted. | Drug: PC14586<br>* 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).<br>|
| Experimental: Part 1 Sequence B<br>Period 1 will be fasted, then washout, then Period 2 will be fed. | Drug: PC14586<br>* 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).<br>|
| Experimental: Part 2 Sequence C<br>Period 1 will be fed, then washout, then Period 2 will be fasted. A different dose of PC14586 will be tested. | Drug: PC14586<br>* 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).<br>|
| Experimental: Part 2 Sequence D<br>Period 1 will be fasted, then washout, then Period 2 will be fed. A different dose of PC14586 will be tested. | Drug: PC14586<br>* 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).<br>|
| Experimental: Part 2 Japanese Cohort<br>6 Japanese participants will be administered a single dose of PC14586. | Drug: PC14586<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Y220C, PC14586, PMV Pharma, PMV, food effect, Pharmacokinetics, Japanese