A Study to Learn About How Itraconazole Affects the Blood Level of Study Medicine (PF-07817883) in Healthy Adults.

A Phase 1, Open-Label, 2-Period, Fixed Sequence Study to Estimate the Effect of Itraconazole on the Pharmacokinetics of PF-07817883 in Healthy Adults

The purpose of this study is to learn how Itraconazole affects the blood level of PF-07817883 in Healthy Adults.

This study is seeking participants who are:

• male and female aged 18 to 65 years old,
• overtly healthy. This can be determined my medical evaluation, medical history, lab tests etc.

This study will consist of 2 parts, Period 1 and Period 2.

Period 1: participants will take PF-07817883 one time by mouth at the study clinic.

Period 2: participants will take PF-07817883 one time by mouth at the study clinic. They will also take daily itraconazole by mouth for 7 days.

Participants will stay at the study clinic for 2 weeks in total. The study doctors will collect blood and urine samples from everyone. The study doctors will check participants' reactions to the study medicine for safety measures. There is a follow-up call at 28 to 35 days from the last dose of PF-07817883.

Itraconazole is an approved medicine. It is also a metabolism inhibitor. When taken with some medicines, it affects the actual level of these medicines in the body. This study will compare blood levels of PF-07817883 given with and without Itraconazole. This will help decide safety and right amount for PF-07817883 when given with metabolism inhibitors.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-07817883; Drug: Itraconazole

Detailed Description

This is a Phase 1, open-label, 2-period, fixed sequence study to estimate the effect of itraconazole, a strong CYP3A4 inhibitor, on the plasma PK of PF-07817883 in healthy adults. The study will consist of 2 treatments: a single oral dose of PF-07817883 alone and a single oral dose of PF-07817883 in combination with multiple oral doses of itraconazole. The PK and safety will be assessed and compared for single dose of PF-07817883 in period 1 and period 2.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and female participants aged 18 to 65 years of age, inclusive, at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and standard 12-lead ECG.
• BMI of 17.5 to 32 kg/m2; and a total body weight >50 kg (110 lb).
• Capable of giving signed informed consent.

Exclusion Criteria:

• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, CV, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
• Positive test result for SARS-CoV-2 infection at admission.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1; The treatment arm includes a single dose of PF-07817883 (Period 1 Day 1)	Drug: PF-07817883; Single oral dose (period 1) or co-administered with itraconazole (period 2)
Experimental: Period 2; This treatment arm includes 7-day dosing of itraconazole with a single dose of PF-07817883 Co-administered on Day 4 (Period 2 Day 4)	Drug: PF-07817883; Single oral dose (period 1) or co-administered with itraconazole (period 2); Drug: Itraconazole; Interacting drug which will be given for 7 days in period 2; Other Names: Sporanox®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of PF-07817883	Cmax was observed directly from data and measured in nanogram per milliliter (ng/mL).	Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4
Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883	AUCinf was derived by AUClast + (Clast*/kel). AUClast was area under the plasma concentration-time profile from time 0 to the time of Clast; 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 loglinear concentration-time curve. AUCinf was measured in nanogram*hour per milliliter (ng*hr/mL).	Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. TEAEs were events that occurred between first dose of study intervention and up to maximum of 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	Day 1 of dosing up to 35 days post last dose of study intervention (maximum up to 48 days)
Number of Participants With Laboratory Test Abnormalities	Laboratory assessments included: hematology assessments included monocytes/leukocytes (percentage [%]) greater than (>) 1.2*upper limit of normal (ULN), urinalysis assessments included urine hemoglobin greater than or equal to (>=) 1, low power field (LPF), urine bacteria >20/LPF.	Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)
Number of Participants With Electrocardiogram (ECG) Findings Per Pre-defined Criteria	Standard 12-lead ECGs was collected using an ECG system that automatically calculates the heart rate (HR) and measures PR interval, QT interval, QTcF, and QRS interval. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. To ensure safety of the participants, a qualified individual at the investigator site made comparisons to baseline measurements. Pre-defined criteria was defined as 30 milliseconds (ms) less than (<) change less than or equal to (<=) 60 ms.	Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)
Number of Participants With Vital Signs Findings Per Pre-defined Criteria	Vital signs included: supine diastolic blood pressure (DBP) measured in millimetre of mercury (mmHg) with criteria value as follows- Value <50 mmHg, change>= 20 mmHg increase, change >= 20 mmHg decrease; supine pulse rate (PR) measured in beats per minute (bpm) with criteria values as follows- value < 40 bpm, value > 120 bpm; supine systolic blood pressure (SBP, mmHg) with criteria values as follows- value< 90 mmHg, change >= 30 mmHg increase, change >=30 mmHg decrease. Vital signs (SBP BP, and pulse rate) were measured with participants after having a rest for at least 5 minutes in a supine position. Supine BP was measured with the participant's arm supported at the level of the heart and recorded to the nearest mmHg after approximately 5 minutes of rest. If timing of these measurements coincided with a blood collection, BP and PR were obtained prior to nominal time of blood collection. Only participants having at least 1 vital sign findings per pre-defined criteria are reported.	Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)
Number of Participants With Clinically Significant Abnormalities in Physical Examination	A complete physical examination included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief physical examination included, at a minimum, assessments of general appearance, the respiratory and CV systems, and participant-reported symptoms. Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner as acceptable according to local regulation. Clinical significance of physical examination abnormalities was judged by physicians.	Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)
Time to Reach Cmax (Tmax) of PF-07817883	Tmax is the time taken (in hours) to reach the maximum serum drug concentration. Tmax was observed directly from data as time of first occurrence.	Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4
Terminal Phase Half-Life (t1/2) of PF-07817883	Terminal half-life was defined as the time measured for the plasma concentration of drug to decrease by one half. t1/2 was determined by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.	Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4
Apparent Clearance (CL/F) of PF-07817883	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf).	Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4
Apparent Volume of Distribution (Vz/F) of PF-07817883	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.	Period 1: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 1; Period 2: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose on Day 4

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2023
• Primary Completion (Actual): July 10, 2023
• Study Completion (Actual): July 10, 2023

Study Registration Dates

• First Submitted: April 10, 2023
• First Submitted That Met QC Criteria: April 10, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: C5091008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No