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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06054464
• Other study ID #: PMV-586-104
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 19, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: September 2023
• Source: PMV Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 28
• Est. completion date: June 30, 2024
• Est. primary completion date: November 3, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• PC14586
Part 1 and Part 2: Single, oral dose of PC14586 on day 1 and single, oral dose of PC14586 on day 14.
• Rabeprazole
Part 1: Daily oral dose of rabeprazole on days 11-14.
• Famotidine
Part 2: Twice daily oral dose of famotidine on days 11-13. Single, oral dose of famotidine on day 14.

Locations

Country	Name	City	State
United States	Parexel International	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
PMV Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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