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

NCT06054464 | Completed Phase 1 FDA Drug

• 1 other identifier: PMV-586-104
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Keywords

Y220C; PC14586; PMV Pharma; PMV; Acid Reducing Agent; p53; DDI; Phase 1; p53 mutation; TP53 mutation; TP53; p53 mutant; p53 reactivator

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (22)

• Part 1: Characterize the total drug exposure from time zero to 24 hours (AUC0-24) for PC14586 when co-administered with rabeprazole.

  20 days

• Part 1: Characterize the total drug exposure from time zero to 96 hours (AUC0-96) for PC14586 when co-administered rabeprazole.

  20 days

• Part 1: Characterize the percent AUCinf due to extrapolation beyond tlast (AUC%extrap) for PC14586 when co-administered with rabeprazole.

  20 days

• Part 1: Characterize the half-life (t1/2) for PC14586 when co-administered with rabeprazole.

  20 days

• Part 1: Characterize the clearance (CL/F) for PC14586 when co-administered orally with rabeprazole.

  20 days

Study Arms (2)

Part 1: PC14586 and rabeprazole

EXPERIMENTAL

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; Drug: Rabeprazole

Part 2: PC14586 and famotidine

EXPERIMENTAL

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; Drug: Famotidine

Interventions

PC14586 DRUG

Part 1 and Part 2: Single, oral dose of PC14586 on day 1 and single, oral dose of PC14586 on day 14.

Part 1: PC14586 and rabeprazole; Part 2: PC14586 and famotidine

Rabeprazole DRUG

Part 1: Daily oral dose of rabeprazole on days 11-14.

Part 1: PC14586 and rabeprazole

Famotidine DRUG

Part 2: Twice daily oral dose of famotidine on days 11-13. Single, oral dose of famotidine on day 14.

Part 2: PC14586 and famotidine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Participants with significant history or clinical manifestation of any medical condition, disease or disorder, as determined by the Investigator.
• Positive hepatitis panel and/or positive human immunodeficiency virus test.
• Use or intend to use any prescription and/or nonprescription medications/products within 14 days prior to check-in.
• Participation in a clinical study involving last administration of an investigational drug within the past 30 days prior to screening.
• Participant has blood pressure \> 140 mm systolic or \> 90 mm diastolic at Screening or Day - 1.
• Participants with a germline TP53 Y220C mutation at Screening.
• 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.
• Participant has history of alcohol and/or illicit drug abuse within 5 years of Screening.
• 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.
• 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.
• 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).

Sponsors & Collaborators

• PMV Pharmaceuticals, Inc: lead

Study Sites (1)

Parexel International

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Interventions

Rabeprazole; Famotidine

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Azoles

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The treatment duration will be up to: 1 day for Treatment Period 1 (PC14586) and 4 days for Treatment Period 2 (PC14586 + ARA) for Parts 1 and 2.

Study Record Dates

• First Submitted: September 8, 2023
• First Posted: September 26, 2023
• Study Start: September 19, 2023
• Primary Completion: November 3, 2023
• Study Completion: February 6, 2024
• Last Updated: November 13, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)