A Study to Understand the Effect of Itraconazole on the Levels of a Study Medicine Called ARV-471 in Healthy Adults

NCT05538312 | Completed Phase 1 Results

• 2 other identifiers: C48910092022-003282-38
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to understand if a strong CYP3A4 inhibitor (itraconazole) affects how ARV-471 is processed and eliminated in healthy adults. All participants in this study will receive one dose of ARV-471 alone by mouth in Period 1. In Period 2, everyone will receive itraconazole by mouth once a day for multiple days. Participants will also receive one dose of ARV-471 by mouth. The levels of ARV-471 in Period 1 will be compared to the levels of ARV-471 in Period 2 to determine if the CYP3A4 inhibitor affects how ARV-471 is processed differently in healthy adults.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of ARV-471

  AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of ARV-471. AUCinf was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) of ARV-471

  Cmax was defined as maximum plasma concentration. Cmax of ARV-471 was observed directly from data.

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

• Area Under the Plasma Concentration-Time Profile From Time 0 to 120 Hours (AUC120) of ARV-473

  ARV-473 was the epimer of ARV-471. AUC120 was defined as area under the plasma concentrationtime profile from time zero to 120 hours. AUC120 was calculate by Linear/Log trapezoidal method.

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose

• Cmax of ARV-473

  ARV-473 was the epimer of ARV-471. Cmax was defined as maximum plasma concentration. Cmax of ARV-473 was observed directly from data.

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

Secondary Outcomes (12)

• Area Under the Plasma Concentration Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of ARV-471

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

• AUC120 of ARV-471

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose

• Time for Cmax (Tmax) of ARV-471

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

• Terminal Half-Life (t1/2) of ARV-471

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

• Apparent Clearance After Oral Dose (CL/F) of ARV-471

  Period 1 Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose; Period 2 Day 5: pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose

Study Arms (1)

vepdegestrant with and without itraconazole

EXPERIMENTAL

vepdegestrant administered as a single dose in Period 1 and Period 2. Itraconazole administered once a day for 11 days in Period 2.

Drug: vepdegestrant; Drug: Itraconazole

Interventions

vepdegestrant DRUG

Participants will receive a single dose of vepdegestrant by mouth in Period 1 and Period 2, with a washout period of at least 10 days between doses of vepdegestrant

Also known as: ARV-471, PF-07850327

vepdegestrant with and without itraconazole

Itraconazole DRUG

Participants will receive itraconazole by mouth once a day for 11 days in Period 2.

Also known as: Sporanox

vepdegestrant with and without itraconazole

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male and/or female participants of non-childbearing potential who are overtly healthy as determined by medical evaluation including medical history, physical exam, laboratory tests, vital signs and standard 12-lead ECGs and are between the ages of 18 and 65 years, inclusive at the time of signing the informed consent document.
• Body Mass Index of 17.5 to 30.5 kg/meters squared; and a body weight \>50 kg.
• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Pregnant female participants, breastfeeding female participants, female participants of childbearing potential.
• Male participants with partners currently pregnant; male participants who are unwilling or unable to use a highly effective method of contraception.
• Use of prescription or non-prescription medications, including vitamins, herbal and dietary supplements, grapefruit/grapefruit containing products, and Seville orange/Seville orange containing products within 7 days prior to the first dose of study intervention with the exception of:
• Moderate/potent CYP3A inducers which are prohibited within 14 days plus 5 half-lives (whichever is longer) prior to the first dose of study intervention.
• Moderate/potent CYP3A inhibitors which are prohibited within 14 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
• Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• A positive urine drug test or alcohol breath test at discretion of investigator.
• Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest.
• Standard 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
• Aspartate transaminase or alanine aminotransferase level ≥ 1.0 × upper limit of normal.
• Total bilirubin level \>1.0 × upper limit of normal; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ upper limit of normal.
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
• History of use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes/day or 2 chews of tobacco/day.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.

Sponsors & Collaborators

• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (1)

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Itraconazole

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

AUCinf for ARV-473 could only be reported for 2 of 12 participants in Period 1 (ARV-471 alone) and 6 of 12 participants in Period 2 (ARV-471 + itraconazole) based on protocol prespecified criteria, therefore was not used as the primary endpoint for ARV-473. Furthermore, AUC120, was selected as the primary endpoint for ARV-473 in lieu of AUClast to account for the difference in sampling intervals between Test Treatment (0-168 hours) and Reference Treatment (0-120 hours).

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 8, 2022
• First Posted: September 13, 2022
• Study Start: February 23, 2023
• Primary Completion: April 24, 2023
• Study Completion: May 22, 2023
• Last Updated: September 23, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)