A Study to Investigate the Effects of Itraconazole on the Pharmacokinetics of PC14586 in Healthy Participants

NCT06362642 | Completed Phase 1 FDA Drug

• 1 other identifier: PMV-586-105
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effect of PC14586 pharmacokinetics when co administered with itraconazole in healthy participants.

Conditions

Healthy Volunteers

Keywords

Y220C; PC14586; PMV Pharma; PMV; itraconazole; rezatapopt; Phase 1; CYP3A4

Outcome Measures

Primary Outcomes (6)

• Characterize the Maximum Plasma Concentration (Cmax) of PC14586 when co-administered with itraconazole in healthy participants.

  Determine the Cmax of PC14586 when co-administered with itraconazole in plasma.

  6 weeks

• Characterize the total drug exposure (AUC0-inf) of PC14586 when co-administered with itraconazole in healthy participants.

  Determine the AUC0-inf of PC14586 when co-administered with itraconazole in plasma.

  6 weeks

• Characterize the time to peak drug concentration (Tmax) of PC14586 when co-administered with itraconazole in healthy participants.

  Determine the Tmax of PC14586 when co-administered with itraconazole in plasma.

  6 weeks

• Characterize the total drug exposure from time zero to 24 hours (AUC0-24) of PC14586 when co-administered with itraconazole in healthy participants.

  Determine the AUC0-24 of PC14586 when co-administered with itraconazole in plasma.

  6 weeks

• Characterize the total drug exposure from time zero to the last timepoint (AUC0-t) of PC14586 when co-administered with itraconazole in healthy participants.

  Determine the AUC0-t of PC14586 when co-administered with itraconazole in plasma.

  6 weeks

• Characterize the half-life (t1/2) of PC14586 when co-administered with itraconazole in healthy participants.

  Determine the t1/2 of PC14586 when co-administered with itraconazole in plasma.

  6 weeks

Secondary Outcomes (10)

• Characterize the Maximum Plasma Concentration (Cmax) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.

  6 weeks

• Characterize the total drug exposure (AUC0-inf) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.

  6 weeks

• Characterize the time to peak drug concentration (Tmax) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.

  6 weeks

• Characterize the total drug exposure from time zero to 24 hours (AUC0-24) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.

  6 weeks

• Characterize the total drug exposure from time zero to the last timepoint (AUC0-t) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.

  6 weeks

Study Arms (1)

PC14586 and Itraconazole

EXPERIMENTAL

Healthy participants will receive a single, oral dose of PC14586 on day 1. On day 20, participants will receive BID oral doses of itraconazole. On days 21-22, participants will receive a single, oral dose of itraconazole. On day 23, participants will receive a single, oral dose of PC14586 and a single oral dose of itraconazole. On days 24-27, participants will receive a single, oral dose of itraconazole.

Drug: PC14586; Drug: Itraconazole

Interventions

PC14586 DRUG

First-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.

Also known as: rezatapopt

PC14586 and Itraconazole

Itraconazole DRUG

Antifungal treatment that is a potent inhibitor of CYP3A4.

PC14586 and Itraconazole

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, aged 18-55 years of age, with BMI between 18.0 and 32.0 kg/m2 inclusive.
• In good health, determined by no clinically significant findings from medical history and evaluations at screening and check-in as assessed by the investigator.
• Females of non-childbearing potential, males who agree to a highly effective method of contraception from first dose through 3 months after end of study visit.
• Participants who are able to swallow tablets and capsules.
• Participants who are capable and willing of giving signed informed consent.

You may not qualify if:

• Participants with significant medical history or clinical manifestation of any medical condition, disease or disorder, as determined by the investigator.
• History of significant hypersensitivity, intolerance, or allergy to itraconazole or any of the excipients or to medicinal products with similar chemical structures, food or other substance.
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs.
• Participant has blood pressure \>140 mmHg systolic or \>90 mmHg diastolic at screening or Day -1.
• Prolonged QT interval corrected for heart rate using Fridericia's correction \>450 ms for males and \>470 ms for females at screening.
• Positive hepatitis panel and/or positive human immunodeficiency virus test.
• Abnormalities in liver function test ALT or AST \>1.5 × upper limit of normal.
• Administration of any vaccine including coronavirus disease 2019 vaccine in the past 14 days prior to check-in.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to check-in.
• Use or intend to use any prescription medications/products or any nonprescription medications/products within 14 days prior to check-in.
• Participation in a clinical study involving last administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing, or within 5 half-lives of the IMP, whichever is longer, or have previously received PC14586.
• Participant has a history of alcohol or drug/chemical abuse within 2 years prior to check-in and/or is unwilling to avoid use of caffeine or alcohol or caffeine-containing foods or alcohol-containing foods, medications, or beverages, within 48 hours prior to check-in until the follow up visit.
• Use of tobacco- or nicotine-containing products (cigarettes, snuff, chewing tobacco, cigars, pipes, vaporizer, or nicotine-replacement products such as nicotine chewing gum and nicotine patches) within 3 months prior to check-in, or positive cotinine at screening or check-in.
• Participants with a germline TP53 Y220C mutation at Screening.

Sponsors & Collaborators

• PMV Pharmaceuticals, Inc: lead

Study Sites (1)

Fortrea

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Design

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

Model Details: The treatments will be: Day 1: single oral dose of PC14586, Day 20: oral dose of itraconazole BID, Day 21-22: single oral dose of itraconazole QD, Day 23: single oral dose of PC14586 and single oral dose of itraconazole, Day 24-27: single oral dose of itraconazole QD.

Study Record Dates

• First Submitted: March 25, 2024
• First Posted: April 12, 2024
• Study Start: March 28, 2024
• Primary Completion: October 22, 2024
• Study Completion: October 22, 2024
• Last Updated: November 13, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)