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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-07817883
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1<br>The treatment arm includes a single dose of PF-07817883 (Period 1 Day 1) | Drug: PF-07817883<br>* Single oral dose (period 1) or co-administered with itraconazole (period 2)<br>|
| Experimental: Period 2<br>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<br>* Single oral dose (period 1) or co-administered with itraconazole (period 2)<br>Drug: Itraconazole<br>* Interacting drug which will be given for 7 days in period 2<br>* Other names: Sporanox®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax ratio of PF-07817883 alone vs coadministration with itraconazole | The ratio of maximum plasma concentration of PF-07817883 following single dose co-administered with itraconazole vs given alone | 0 to 96 hours post PF-07817883 | 
| AUC ratio of PF-07817883 alone vs coadministration with itraconazole | The ratio of AUC (area under plasma concentration curve) of PF-07817883 following single dose co-administered with itraconazole vs given alone | 0 to 96 hours post PF-07817883 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment Emergent Adverse Events (TEAE) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment | Time the participant provides informed consent through and including follow-up contact occurring up to 35 days after the last administration of the study intervention | 
| Number of Participants With Laboratory Abnormalities | Laboratory examination includes hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose);urinalysis (decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin]). | Baseline (Study Day -28 to -1) up to Period 2 Day 8 (Study Day 13) | 
| Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG | Baseline (Study Day -28 to -1) up to Period 2 Day 8 (Study Day 13) | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate. | Baseline (Study Day -28 to -1) up to Period 2 Day 8 (Study Day 13) | 
| Number of Participants With Clinically Significant findings in physical exam | A complete physical examination will include, 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 will include, at a minimum, assessments of general appearance, the respiratory and CV systems, and participant-reported symptoms. | Baseline (Study Day -28 to -1) | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07817883, when administered alone | Observed directly from data | Period 1 - Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07817883, when administered with itraconazole | Observed directly from data | Period 2 Day 4 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours after PF-07817883 dose | 
| Plasma Decay Half-Life (t1/2) of PF-07817883, when administered alone | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Period 1 - Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose | 
| Plasma Decay Half-Life (t1/2) of PF-07817883, when administered with itraconazole | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Period 2 Day 4 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours after PF-07817883 dose | 
| Apparent Oral Clearance (CL/F) of PF-07817883, when administered alone | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Period 1 - Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose | 
| Apparent Oral Clearance (CL/F) of PF-07817883, when administered with itraconazole | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Period 2 Day 4 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours after PF-07817883 dose | 
| Apparent Volume of Distribution (Vz/F) of PF-07817883, when administered alone | 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. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Period 1 - Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose | 
| Apparent Volume of Distribution (Vz/F) of PF-07817883, when administered with itraconazole | 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. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Period 2 Day 4 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours after PF-07817883 dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19