A Study to Learn About How Itraconazole Affects the Blood Level of Study Medicine (PF-07817883) in Healthy Adults.
Study Details
Study Description
Brief Summary
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:
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male and female aged 18 to 65 years old,
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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 Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Cmax ratio of PF-07817883 alone vs coadministration with itraconazole [0 to 96 hours post PF-07817883]
The ratio of maximum plasma concentration of PF-07817883 following single dose co-administered with itraconazole vs given alone
- AUC ratio of PF-07817883 alone vs coadministration with itraconazole [0 to 96 hours post PF-07817883]
The ratio of AUC (area under plasma concentration curve) of PF-07817883 following single dose co-administered with itraconazole vs given alone
Secondary Outcome Measures
- Number of participants with Treatment Emergent Adverse Events (TEAE) [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]
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
- Number of Participants With Laboratory Abnormalities [Baseline (Study Day -28 to -1) up to Period 2 Day 8 (Study Day 13)]
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]).
- Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings [Baseline (Study Day -28 to -1) up to Period 2 Day 8 (Study Day 13)]
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
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Baseline (Study Day -28 to -1) up to Period 2 Day 8 (Study Day 13)]
Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate.
- Number of Participants With Clinically Significant findings in physical exam [Baseline (Study Day -28 to -1)]
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.
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07817883, when administered alone [Period 1 - Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose]
Observed directly from data
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07817883, when administered with itraconazole [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]
Observed directly from data
- Plasma Decay Half-Life (t1/2) of PF-07817883, when administered alone [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 is the time measured for the plasma concentration to decrease by one half.
- Plasma Decay Half-Life (t1/2) of PF-07817883, when administered with itraconazole [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 is the time measured for the plasma concentration to decrease by one half.
- Apparent Oral Clearance (CL/F) of PF-07817883, when administered alone [Period 1 - Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose]
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.
- Apparent Oral Clearance (CL/F) of PF-07817883, when administered with itraconazole [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]
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.
- Apparent Volume of Distribution (Vz/F) of PF-07817883, when administered alone [Period 1 - Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose]
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.
- Apparent Volume of Distribution (Vz/F) of PF-07817883, when administered with itraconazole [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]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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BMI of 17.5 to 32 kg/m2; and a total body weight >50 kg (110 lb).
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Capable of giving signed informed consent.
Exclusion Criteria:
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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.
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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.
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Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
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Positive test result for SARS-CoV-2 infection at admission.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- C5091008