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

A Phase 1, Open-label, Fixed-sequence Study to Investigate the Effect of Coadministration of Itraconazole on the Pharmacokinetics of PC14586 in Healthy Participants

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

Study Overview

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

Detailed Description

PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.

This is a Phase 1, open-label, fixed-sequence study to investigate the effect of coadministration of itraconazole on the pharmacokinetics (PK) of PC14586 (rezatapopt) in healthy male and female participants. Potential participants will be screened to assess their eligibility to enter the study within 56 days prior to the first dose administration. Participants will be admitted into the study site on Day -1 and be confined to the study site until discharge on Day 33. Participants will return to the study site for PK sample collection on Day 37 and a follow-up visit and PK sample collection on Day 42.

Approximately 16 participants will be enrolled in this study.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Fortrea

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Healthy, non-smoking males and females, aged 18-55 years of age, with BMI between 18.0 and 32.0 kg/m2 inclusive.
2. In good health, determined by no clinically significant findings from medical history and evaluations at screening and check-in as assessed by the investigator.
3. 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.
4. Participants who are able to swallow tablets and capsules.
5. Participants who are capable and willing of giving signed informed consent.

Exclusion Criteria:

1. Participants with significant medical history or clinical manifestation of any medical condition, disease or disorder, as determined by the investigator.
2. 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.
3. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs.
4. Participant has blood pressure >140 mmHg systolic or >90 mmHg diastolic at screening or Day -1.
5. Prolonged QT interval corrected for heart rate using Fridericia's correction >450 ms for males and >470 ms for females at screening.
6. Positive hepatitis panel and/or positive human immunodeficiency virus test.
7. Abnormalities in liver function test ALT or AST >1.5 × upper limit of normal.
8. Administration of any vaccine including coronavirus disease 2019 vaccine in the past 14 days prior to check-in.
9. 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.
10. Use or intend to use any prescription medications/products or any nonprescription medications/products within 14 days prior to check-in.
11. 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.
12. 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.
13. 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.
14. Participants with a germline TP53 Y220C mutation at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PC14586 and Itraconazole; 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; First-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.; Other Names: rezatapopt; Drug: Itraconazole; Antifungal treatment that is a potent inhibitor of CYP3A4.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the Maximum Plasma Concentration (Cmax) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.	Determine the Cmax of PC14586 metabolites M13 and M14 when co-administered with itraconazole in plasma.	6 weeks
Characterize the total drug exposure (AUC0-inf) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.	Determine the AUC0-inf of PC14586 metabolites M13 and M14 when co-administered with itraconazole in plasma.	6 weeks
Characterize the time to peak drug concentration (Tmax) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.	Determine the Tmax of PC14586 metabolites M13 and M14 when co-administered with itraconazole in plasma.	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.	Determine the AUC0-24 of PC14586 metabolites M13 and M14 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 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.	Determine the AUC0-t of PC14586 metabolites M13 and M14 when co-administered with itraconazole in plasma.	6 weeks
Characterize the half-life (t1/2) of PC14586 metabolites M13 and M14 when co-administered with itraconazole in healthy participants.	Determine the t1/2 of PC14586 metabolites M13 and M14 when co-administered with itraconazole in plasma.	6 weeks
Identification of the incidence of treatment emergent adverse events (TEAE) of PC14586 when administered alone and co-administered with itraconazole in healthy participants.	Identify the incidence of TEAEs of PC14586 alone or when co-administered with itraconazole.	6 weeks
Identification of vital sign abnormalities after administration of PC14586 alone and when co-administered with itraconazole in healthy participants.	Identify the number of participants with abnormal vital signs.	6 weeks
Identification of 12-lead electrocardiogram (ECG) abnormalities after administration of PC14586 alone and when co-administered with itraconazole in healthy participants.	Identify the number of participants with abnormal ECG results.	6 weeks
Identification of laboratory abnormalities based on hematology and clinical chemistry after administration of PC14586 alone and when co-administered with itraconazole in healthy participants.	Identify the number of participants with an incidence of laboratory abnormalities in test results.	6 weeks

Collaborators and Investigators

• Sponsor: PMV Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2024
• Primary Completion (Actual): October 22, 2024
• Study Completion (Actual): October 22, 2024

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 12, 2024

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; CYP3A4; itraconazole; PC14586; Y220C; PMV; PMV Pharma; rezatapopt
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP3A Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: PMV-586-105

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