A Study to Investigate the Effects of Acid Reducing Agents on Pharmacokinetics of PC14586 in Healthy Participants

A Phase 1, Open-Label, Non-Randomized, Two-Part, Fixed-Sequence, Study to Evaluate the Effects of Acid Reducing Agents on the Pharmacokinetics of PC14586 in Healthy Volunteers

This study will assess the effect of a Proton Pump Inhibitor (PPI) (rabeprazole) on the pharmacokinetics (PK) of PC14586 and the effect of an H2-receptor antagonist (famotidine) on the PK of PC14586

Study Overview

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

Detailed Description

PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation. This study will investigate the effects of acid reducing agents on the pharmacokinetics of PC14586.

This is a 2-part, open-label, two-period, fixed-sequence study in healthy participants with each participant used as his/her own control to assess the effect of rabeprazole (Part 1) or famotidine (Part 2) on the PK of PC14586. The results from Part 1 will be analyzed before deciding to, if applicable, progress to Part 2. Part 2 of the study will only be initiated if the findings from Part 1 show an interaction or are inconclusive.

Approximately 25 participants will be enrolled in Part 1 and approximately 25 participants will be enrolled in Part 2. The Study timelines reflect both Part 1 and Part 2.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Parexel International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy, non-smoking males and females, 18-55 years of age, with BMI between 18.5 - 30 kg/m2 inclusive.
2. Agree to use a highly effective method of contraception from 14 days before check-in through 90 days after last dose of study drug.
3. Participants who are capable of giving signed informed consent.

Exclusion Criteria:

1. Participants with significant history or clinical manifestation of any medical condition, disease or disorder, as determined by the Investigator.
2. Positive hepatitis panel and/or positive human immunodeficiency virus test.
3. Use or intend to use any prescription and/or nonprescription medications/products within 14 days prior to check-in.
4. Participation in a clinical study involving last administration of an investigational drug within the past 30 days prior to screening.
5. Participant has blood pressure > 140 mm systolic or > 90 mm diastolic at Screening or Day - 1.
6. Participants with a germline TP53 Y220C mutation at Screening.
7. Participant has smoked or used other nicotine-containing products (snuff, chewing tobacco, cigars, pipes, vaporizer, or nicotine-replacement products such as nicotine chewing gum and nicotine plasters) during the 3 months before the Screening Visit.
8. Participant has history of alcohol and/or illicit drug abuse within 5 years of Screening.
9. Participant is unwilling to avoid use of alcohol or alcohol-containing foods, medications, or beverages, 48 hours prior to admission until discharge from the study center.
10. Participant has a history of hypersensitivity to the study drug (PC14586), rabeprazole (Part 1), or famotidine (Part 2) or any of the excipients or to medicinal products with similar chemical structures.
11. Female participant that is breastfeeding (or bottle feeding with their breast milk) or female participant with a positive serum pregnancy test at the Screening Visit or positive serum or urine pregnancy test at Day -1 (admission).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: PC14586 and rabeprazole; Healthy participants will receive a single, oral dose of PC14586 on day 1. On days 11-13, participants will receive an oral daily dose of rabeprazole. On day 14, participants will receive a co-administration dose of rabeprazole and PC14586. Rabeprazole will be given 1 hour prior to PC14586. Participants will be given a low-fat meal 30 minutes prior to PC14586 dosing.	Drug: PC14586; Part 1 and Part 2: Single, oral dose of PC14586 on day 1 and single, oral dose of PC14586 on day 14.; Drug: Rabeprazole; Part 1: Daily oral dose of rabeprazole on days 11-14.
Experimental: Part 2: PC14586 and famotidine; Healthy participants will receive a single, oral dose of PC14586 on day 1. On days 11-13, participants will receive a twice daily, oral dose of famotidine. On day 14, participants will receive PC14586 two hours before a dose of famotidine. Participants will be given a low-fat meal 30 minutes prior to PC14586 dosing.	Drug: PC14586; Part 1 and Part 2: Single, oral dose of PC14586 on day 1 and single, oral dose of PC14586 on day 14.; Drug: Famotidine; Part 2: Twice daily oral dose of famotidine on days 11-13. Single, oral dose of famotidine on day 14.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Characterize the Maximum Plasma Concentration (Cmax) of PC14586 when co-administered with rabeprazole.	Determine the Cmax of PC14586 when co-administered with rabeprazole in plasma.	20 days
Part 1: Characterize the total drug exposure to the last measurable concentration (AUC0-last) of PC14586 when co-administered with rabeprazole.	Determine the AUC0-last of PC14586 when co-administered with rabeprazole in plasma.	20 days
Part 1: Characterize the total drug exposure (AUC0-inf) of PC14586 when co-administered with rabeprazole.	Determine the AUC0-inf of PC14586 when co-administered with rabeprazole in plasma.	20 days
Part 1: Characterize the time to peak drug concentration (Tmax) of PC14586 when co-administered with rabeprazole.	Determine the Tmax of PC14586 when co-administered with rabeprazole in plasma.	20 days
Part 2: Characterize the Maximum Plasma Concentration (Cmax) of PC14586 when co-administered with famotidine.	Determine the Cmax of PC14586 when co-administered with famotidine in plasma.	20 days
Part 2: Characterize the total drug exposure to the last measurable concentration (AUC0-last) of PC14586 when co-administered with famotidine.	Determine the AUC0-last of PC14586 when co-administered with famotidine in plasma.	20 days
Part 2: Characterize the total drug exposure (AUC0-inf) of PC14586 when co-administered with famotidine.	Determine the AUC0-inf of PC14586 when co-administered with famotidine in plasma.	20 days
Part 2: Characterize the time to peak drug concentration (Tmax) of PC14586 when co-administered with famotidine.	Determine the Tmax of PC14586 when co-administered with famotidine in plasma.	20 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Characterize the total drug exposure from time zero to 24 hours (AUC0-24) for PC14586 when co-administered with rabeprazole.	Determine the AUC0-24 of PC14586 when co-administered with rabeprazole in plasma.	20 days
Part 1: Characterize the total drug exposure from time zero to 96 hours (AUC0-96) for PC14586 when co-administered rabeprazole.	Determine the AUC0-96 of PC14586 when co-administered with rabeprazole in plasma.	20 days
Part 1: Characterize the percent AUCinf due to extrapolation beyond tlast (AUC%extrap) for PC14586 when co-administered with rabeprazole.	Determine the AUC%extrap of PC14586 when co-administered with rabeprazole in plasma.	20 days
Part 1: Characterize the half-life (t1/2) for PC14586 when co-administered with rabeprazole.	Determine the t1/2 of PC14586 when co-administered with rabeprazole in plasma.	20 days
Part 1: Characterize the clearance (CL/F) for PC14586 when co-administered orally with rabeprazole.	Determine the CL/F of PC14586 when co-administered orally with rabeprazole in plasma.	20 days
Part 1: Characterize the volume of distribution (Vz/F) for PC14586 when co-administered orally with rabeprazole.	Determine the Vz/F of PC14586 when co-administered orally with rabeprazole in plasma.	20 days
Part 1: Characterize the apparent terminal elimination rate (lambda Z) for PC14586 when co-administered orally with rabeprazole.	Determine the lambda Z of PC14586 when co-administered orally with rabeprazole in plasma.	20 days
Part 1: Identification of the Incidence of treatment emergent adverse events (TEAE) for PC14586 alone or when co-administered with rabeprazole.	Identify the incidence of TEAEs of PC14586 alone or when co-administered orally with rabeprazole in plasma.	20 days
Part 1: Identification of vital sign abnormalities after administration of PC14586 alone or when co-administered with rabeprazole.	Number of participants with abnormal vital signs.	20 days
Part 1: Identification of 12-lead electrocardiogram (ECG) abnormalities after administration of PC14586 alone or when co-administered with rabeprazole.	Number of participants with abnormal ECG results.	20 days
Part 1: Identification of laboratory abnormalities based on hematology and clinical chemistry after administration of PC14586 alone or when co-administered with rabeprazole.	Number of participants with an incidence of laboratory abnormalities in test results.	20 days
Part 2: Characterize the total drug exposure from time zero to 24 hours (AUC0-24) for PC14586 when co-administered with famotidine.	Determine the AUC0-24 of PC14586 when co-administered with famotidine in plasma.	20 days
Part 2: Characterize the total drug exposure from time zero to 96 hours (AUC0-96) for PC14586 when co-administered with famotidine.	Determine the AUC0-96 of PC14586 when co-administered with famotidine in plasma.	20 days
Part 2: Characterize the percent AUCinf due to extrapolation beyond tlast (AUC%extrap) for PC14586 when co-administered with famotidine.	Determine the AUC%extrap of PC14586 when co-administered with famotidine in plasma.	20 days
Part 2: Characterize the half-life (t1/2) for PC14586 when co-administered with famotidine.	Determine the t1/2 of PC14586 when co-administered with famotidine in plasma.	20 days
Part 2: Characterize the clearance (CL/F) for PC14586 when co-administered orally with famotidine.	Determine the CL/F of PC14586 when co-administered orally with famotidine in plasma.	20 days
Part 2: Characterize the volume of distribution (Vz/F) for PC14586 when co-administered orally with famotidine.	Determine the Vz/F of PC14586 when co-administered orally with famotidine in plasma.	20 days
Part 2: Characterize the apparent terminal elimination rate (lambda Z) for PC14586 when co-administered orally with famotidine.	Determine the lambda Z of PC14586 when co-administered orally with famotidine in plasma.	20 days
Part 2: Identification of the Incidence of treatment emergent adverse events (TEAE) for PC14586 alone or when co-administered with famotidine.	Identify the incidence of TEAEs of PC14586 alone or when co-administered orally with famotidine in plasma.	20 days
Part 2: Identification of vital sign abnormalities after administration of PC14586 alone or when co-administered with famotidine.	Number of participants with abnormal vital signs.	20 days
Part 2: Identification of 12-lead electrocardiogram (ECG) abnormalities after administration of PC14586 alone or when co-administered with famotidine.	Number of participants with abnormal ECG results.	20 days
Part 2: Identification of laboratory abnormalities based on hematology and clinical chemistry after administration of PC14586 alone or when co-administered with famotidine.	Number of participants with an incidence of laboratory abnormalities in test results.	20 days

Collaborators and Investigators

• Sponsor: PMV Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2023
• Primary Completion (Actual): November 3, 2023
• Study Completion (Actual): February 6, 2024

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Estimated): November 13, 2024
• Last Update Submitted That Met QC Criteria: November 11, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Phase 1; p53 mutation; p53; TP53; DDI; Acid Reducing Agent; PC14586; Y220C; PMV; PMV Pharma; TP53 mutation; p53 mutant; p53 reactivator
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Inhibitors; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Histamine H2 Antagonists; Rabeprazole; Famotidine
• Other Study ID Numbers: PMV-586-104

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
• product manufactured in and exported from the U.S.: No