Clinical trial NCT05538312: A Study to Understand the Effect of Itraconazole on the Levels of a Study Medicine Called ARV-471 in Healthy Adults
Official title: AN INTERVENTIONAL, PHASE 1, OPEN-LABEL, FIXED SEQUENCE, 2-PERIOD STUDY TO ESTIMATE THE EFFECT OF MULTIPLE DOSES OF ITRACONAZOLE ON THE PHARMACOKINETICS OF SINGLE DOSE ARV-471 IN THE FED CONDITION IN HEALTHY ADULT MALES, AND FEMALES OF NONCHILDBEARING POTENTIAL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Arvinas Estrogen Receptor, Inc.
First posted: 2022-09-13
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* Known hypersensitivity or previous adverse events associated with azole antifungals or any of the formulation components of ARV-471.
* History of sensitivity to heparin or heparin induced thrombocytopenia.
* Estimated glomerular filtration rate \<60 mL/min/1.73m2.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of ARV-471
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of ARV-471
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Profile From Time 0 to 120 Hours (AUC120) of ARV-473
timeFrame: 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
measure: Cmax of ARV-473
timeFrame: 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:
measure: Area Under the Plasma Concentration Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of ARV-471
timeFrame: 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
measure: AUC120 of ARV-471
timeFrame: 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
measure: Time for Cmax (Tmax) of ARV-471
timeFrame: 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
measure: Terminal Half-Life (t1/2) of ARV-471
timeFrame: 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
measure: Apparent Clearance After Oral Dose (CL/F) of ARV-471
timeFrame: 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
measure: Apparent Volume of Distribution After Oral Dose (Vz/F) of ARV-471
timeFrame: 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
measure: AUClast of ARV-473
timeFrame: 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
measure: Tmax of ARV-473
timeFrame: 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
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose (Day 1) up to 35 days after the last dose of study intervention (up to 52 days)
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Baseline (Period 1 Day -1) up to Period 2 Day 12 (19 days)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline (Period 1 Day 1) up to Period 2 Day 5 (11 days)
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline (Period 1 Day 1) up to Period 2 Day 12 (18 days)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: