A Study to Investigate the Effects of Acid Reducing Agents on Pharmacokinetics of PC14586 in Healthy Participants
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: PC14586 and rabeprazole 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
Part 1 and Part 2: Single, oral dose of PC14586 on day 1 and single, oral dose of PC14586 on day 14.
Drug: Rabeprazole
Part 1: Daily oral dose of rabeprazole on days 11-14.
|
| Experimental: Part 2: PC14586 and famotidine 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
Part 1 and Part 2: Single, oral dose of PC14586 on day 1 and single, oral dose of PC14586 on day 14.
Drug: Famotidine
Part 2: Twice daily oral dose of famotidine on days 11-13. Single, oral dose of famotidine on day 14.
|
Outcome Measures
Primary Outcome Measures
- Part 1: Characterize the Maximum Plasma Concentration (Cmax) of PC14586 when co-administered with rabeprazole. [20 days]
Determine the Cmax of PC14586 when co-administered with rabeprazole in plasma.
- Part 1: Characterize the total drug exposure to the last measurable concentration (AUC0-last) of PC14586 when co-administered with rabeprazole. [20 days]
Determine the AUC0-last of PC14586 when co-administered with rabeprazole in plasma.
- Part 1: Characterize the total drug exposure (AUC0-inf) of PC14586 when co-administered with rabeprazole. [20 days]
Determine the AUC0-inf of PC14586 when co-administered with rabeprazole in plasma.
- Part 1: Characterize the time to peak drug concentration (Tmax) of PC14586 when co-administered with rabeprazole. [20 days]
Determine the Tmax of PC14586 when co-administered with rabeprazole in plasma.
- Part 2: Characterize the Maximum Plasma Concentration (Cmax) of PC14586 when co-administered with famotidine. [20 days]
Determine the Cmax of PC14586 when co-administered with famotidine in plasma.
- Part 2: Characterize the total drug exposure to the last measurable concentration (AUC0-last) of PC14586 when co-administered with famotidine. [20 days]
Determine the AUC0-last of PC14586 when co-administered with famotidine in plasma.
- Part 2: Characterize the total drug exposure (AUC0-inf) of PC14586 when co-administered with famotidine. [20 days]
Determine the AUC0-inf of PC14586 when co-administered with famotidine in plasma.
- Part 2: Characterize the time to peak drug concentration (Tmax) of PC14586 when co-administered with famotidine. [20 days]
Determine the Tmax of PC14586 when co-administered with famotidine in plasma.
Secondary Outcome Measures
- Part 1: Characterize the total drug exposure from time zero to 24 hours (AUC0-24) for PC14586 when co-administered with rabeprazole. [20 days]
Determine the AUC0-24 of PC14586 when co-administered with rabeprazole in plasma.
- Part 1: Characterize the total drug exposure from time zero to 96 hours (AUC0-96) for PC14586 when co-administered rabeprazole. [20 days]
Determine the AUC0-96 of PC14586 when co-administered with rabeprazole in plasma.
- Part 1: Characterize the percent AUCinf due to extrapolation beyond tlast (AUC%extrap) for PC14586 when co-administered with rabeprazole. [20 days]
Determine the AUC%extrap of PC14586 when co-administered with rabeprazole in plasma.
- Part 1: Characterize the half-life (t1/2) for PC14586 when co-administered with rabeprazole. [20 days]
Determine the t1/2 of PC14586 when co-administered with rabeprazole in plasma.
- Part 1: Characterize the clearance (CL/F) for PC14586 when co-administered orally with rabeprazole. [20 days]
Determine the CL/F of PC14586 when co-administered orally with rabeprazole in plasma.
- Part 1: Characterize the volume of distribution (Vz/F) for PC14586 when co-administered orally with rabeprazole. [20 days]
Determine the Vz/F of PC14586 when co-administered orally with rabeprazole in plasma.
- Part 1: Characterize the apparent terminal elimination rate (lambda Z) for PC14586 when co-administered orally with rabeprazole. [20 days]
Determine the lambda Z of PC14586 when co-administered orally with rabeprazole in plasma.
- Part 1: Identification of the Incidence of treatment emergent adverse events (TEAE) for PC14586 alone or when co-administered with rabeprazole. [20 days]
Identify the incidence of TEAEs of PC14586 alone or when co-administered orally with rabeprazole in plasma.
- Part 1: Identification of vital sign abnormalities after administration of PC14586 alone or when co-administered with rabeprazole. [20 days]
Number of participants with abnormal vital signs.
- Part 1: Identification of 12-lead electrocardiogram (ECG) abnormalities after administration of PC14586 alone or when co-administered with rabeprazole. [20 days]
Number of participants with abnormal ECG results.
- Part 1: Identification of laboratory abnormalities based on hematology and clinical chemistry after administration of PC14586 alone or when co-administered with rabeprazole. [20 days]
Number of participants with an incidence of laboratory abnormalities in test results.
- Part 2: Characterize the total drug exposure from time zero to 24 hours (AUC0-24) for PC14586 when co-administered with famotidine. [20 days]
Determine the AUC0-24 of PC14586 when co-administered with famotidine in plasma.
- Part 2: Characterize the total drug exposure from time zero to 96 hours (AUC0-96) for PC14586 when co-administered with famotidine. [20 days]
Determine the AUC0-96 of PC14586 when co-administered with famotidine in plasma.
- Part 2: Characterize the percent AUCinf due to extrapolation beyond tlast (AUC%extrap) for PC14586 when co-administered with famotidine. [20 days]
Determine the AUC%extrap of PC14586 when co-administered with famotidine in plasma.
- Part 2: Characterize the half-life (t1/2) for PC14586 when co-administered with famotidine. [20 days]
Determine the t1/2 of PC14586 when co-administered with famotidine in plasma.
- Part 2: Characterize the clearance (CL/F) for PC14586 when co-administered orally with famotidine. [20 days]
Determine the CL/F of PC14586 when co-administered orally with famotidine in plasma.
- Part 2: Characterize the volume of distribution (Vz/F) for PC14586 when co-administered orally with famotidine. [20 days]
Determine the Vz/F of PC14586 when co-administered orally with famotidine in plasma.
- Part 2: Characterize the apparent terminal elimination rate (lambda Z) for PC14586 when co-administered orally with famotidine. [20 days]
Determine the lambda Z of PC14586 when co-administered orally with famotidine in plasma.
- Part 2: Identification of the Incidence of treatment emergent adverse events (TEAE) for PC14586 alone or when co-administered with famotidine. [20 days]
Identify the incidence of TEAEs of PC14586 alone or when co-administered orally with famotidine in plasma.
- Part 2: Identification of vital sign abnormalities after administration of PC14586 alone or when co-administered with famotidine. [20 days]
Number of participants with abnormal vital signs.
- Part 2: Identification of 12-lead electrocardiogram (ECG) abnormalities after administration of PC14586 alone or when co-administered with famotidine. [20 days]
Number of participants with abnormal ECG results.
- Part 2: Identification of laboratory abnormalities based on hematology and clinical chemistry after administration of PC14586 alone or when co-administered with famotidine. [20 days]
Number of participants with an incidence of laboratory abnormalities in test results.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
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Participants who are capable of giving signed informed consent.
Exclusion Criteria:
-
Participants with significant history or clinical manifestation of any medical condition, disease or disorder, as determined by the Investigator.
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Positive hepatitis panel and/or positive human immunodeficiency virus test.
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Use or intend to use any prescription and/or nonprescription medications/products within 14 days prior to check-in.
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Participation in a clinical study involving last administration of an investigational drug within the past 30 days prior to screening.
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Participant has blood pressure > 140 mm systolic or > 90 mm diastolic at Screening or Day - 1.
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Participants with a germline TP53 Y220C mutation at Screening.
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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.
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Participant has history of alcohol and/or illicit drug abuse within 5 years of Screening.
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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.
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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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Parexel International | Baltimore | Maryland | United States | 21225 |
Sponsors and Collaborators
- PMV Pharmaceuticals, Inc
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PMV-586-104