Clinical trial NCT06054464: A Study to Investigate the Effects of Acid Reducing Agents on Pharmacokinetics of PC14586 in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: PMV Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2023-09-26
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: OTHER

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

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Part 1: Characterize the Maximum Plasma Concentration (Cmax) of PC14586 when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the total drug exposure to the last measurable concentration (AUC0-last) of PC14586 when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the total drug exposure (AUC0-inf) of PC14586 when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the time to peak drug concentration (Tmax) of PC14586 when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 2: Characterize the Maximum Plasma Concentration (Cmax) of PC14586 when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the total drug exposure to the last measurable concentration (AUC0-last) of PC14586 when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the total drug exposure (AUC0-inf) of PC14586 when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the time to peak drug concentration (Tmax) of PC14586 when co-administered with famotidine.
timeFrame: 20 days
Secondary outcomes:
measure: Part 1: Characterize the total drug exposure from time zero to 24 hours (AUC0-24) for PC14586 when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the total drug exposure from time zero to 96 hours (AUC0-96) for PC14586 when co-administered rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the percent AUCinf due to extrapolation beyond tlast (AUC%extrap) for PC14586 when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the half-life (t1/2) for PC14586 when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the clearance (CL/F) for PC14586 when co-administered orally with rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the volume of distribution (Vz/F) for PC14586 when co-administered orally with rabeprazole.
timeFrame: 20 days
measure: Part 1: Characterize the apparent terminal elimination rate (lambda Z) for PC14586 when co-administered orally with rabeprazole.
timeFrame: 20 days
measure: Part 1: Identification of the Incidence of treatment emergent adverse events (TEAE) for PC14586 alone or when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Identification of vital sign abnormalities after administration of PC14586 alone or when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Identification of 12-lead electrocardiogram (ECG) abnormalities after administration of PC14586 alone or when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 1: Identification of laboratory abnormalities based on hematology and clinical chemistry after administration of PC14586 alone or when co-administered with rabeprazole.
timeFrame: 20 days
measure: Part 2: Characterize the total drug exposure from time zero to 24 hours (AUC0-24) for PC14586 when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the total drug exposure from time zero to 96 hours (AUC0-96) for PC14586 when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the percent AUCinf due to extrapolation beyond tlast (AUC%extrap) for PC14586 when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the half-life (t1/2) for PC14586 when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the clearance (CL/F) for PC14586 when co-administered orally with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the volume of distribution (Vz/F) for PC14586 when co-administered orally with famotidine.
timeFrame: 20 days
measure: Part 2: Characterize the apparent terminal elimination rate (lambda Z) for PC14586 when co-administered orally with famotidine.
timeFrame: 20 days
measure: Part 2: Identification of the Incidence of treatment emergent adverse events (TEAE) for PC14586 alone or when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Identification of vital sign abnormalities after administration of PC14586 alone or when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Identification of 12-lead electrocardiogram (ECG) abnormalities after administration of PC14586 alone or when co-administered with famotidine.
timeFrame: 20 days
measure: Part 2: Identification of laboratory abnormalities based on hematology and clinical chemistry after administration of PC14586 alone or when co-administered with famotidine.
timeFrame: 20 days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Parexel International
state: Maryland
Study officials:
References: