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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05822440

Enrollment

Registered

2023-04-20

Start date

2023-04-13

Completion date

2023-07-10

Last updated

2024-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

COVID-19

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: * 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

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.

Interventions

DRUGPF-07817883

Single oral dose (period 1) or co-administered with itraconazole (period 2)

DRUGItraconazole

Interacting drug which will be given for 7 days in period 2

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Masking description

Masking: None (open label)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Maximum Observed Concentration (Cmax) of PF-07817883	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	Cmax was observed directly from data and measured in nanogram per milliliter (ng/mL).
Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883	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	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).

Secondary

Measure	Time frame	Description
Number of Participants With Electrocardiogram (ECG) Findings Per Pre-defined Criteria	Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)	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.
Number of Participants With Vital Signs Findings Per Pre-defined Criteria	Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)	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.
Number of Participants With Clinically Significant Abnormalities in Physical Examination	Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Day 1 of dosing up to 35 days post last dose of study intervention (maximum up to 48 days)	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.
Terminal Phase Half-Life (t1/2) of PF-07817883	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 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.
Apparent Clearance (CL/F) of PF-07817883	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	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).
Apparent Volume of Distribution (Vz/F) of PF-07817883	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	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.
Time to Reach Cmax (Tmax) of PF-07817883	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	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.
Number of Participants With Laboratory Test Abnormalities	Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)	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.

Countries

United States

Participant flow

Pre-assignment details

A total of 12 participants were enrolled in the study. Study had 2 treatment periods with fixed sequence.

Participants by arm

Arm	Count
All Participants All participants who received PF-07817883 300 mg orally on Day 1 of Period 1 and on Day 4 of Period 2 along with itraconazole 200 mg QD orally from Day 1 to Day 7 of Period 2.	12
Total	12

Baseline characteristics

Characteristic	All Participants
Age, Continuous	38.7 Years STANDARD_DEVIATION 8.48
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	6 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	4 Participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 12	0 / 12
other Total, other adverse events	1 / 12	3 / 12	2 / 12
serious Total, serious adverse events	0 / 12	0 / 12	0 / 12

Outcome results

Primary

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).

Time frame: 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

Population: PK parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-07817883	Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883	21720 ng*hr/mL	Geometric Coefficient of Variation 26
PF-07817883 + Itraconazole	Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883	46400 ng*hr/mL	Geometric Coefficient of Variation 36

Comparison: Ratio was between test to reference, where test is PF-07817883 + Itraconazole arm and reference is PF-07817883 arm. Natural log transformed Cmax of PF-07817883 were analyzed using a mixed effect model with treatment as fixed effect and participant as a random effect. The ratios (and 90% CIs) were expressed as percentages.90% CI: [183.76, 246.5]

Primary

Maximum Observed Concentration (Cmax) of PF-07817883

Cmax was observed directly from data and measured in nanogram per milliliter (ng/mL).

Population: Pharmacokinetic (PK) parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-07817883	Maximum Observed Concentration (Cmax) of PF-07817883	4030 ng/mL	Geometric Coefficient of Variation 28
PF-07817883 + Itraconazole	Maximum Observed Concentration (Cmax) of PF-07817883	4985 ng/mL	Geometric Coefficient of Variation 41

Secondary

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).

Population: PK parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-07817883	Apparent Clearance (CL/F) of PF-07817883	13.81 Liter/Hours	Geometric Coefficient of Variation 26
PF-07817883 + Itraconazole	Apparent Clearance (CL/F) of PF-07817883	6.469 Liter/Hours	Geometric Coefficient of Variation 36

Secondary

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.

Population: PK parameter set included all participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-07817883	Apparent Volume of Distribution (Vz/F) of PF-07817883	100.4 Liter	Geometric Coefficient of Variation 63
PF-07817883 + Itraconazole	Apparent Volume of Distribution (Vz/F) of PF-07817883	86.29 Liter	Geometric Coefficient of Variation 51

Secondary

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.

Time frame: Day 1 of dosing up to last dose of study intervention or early termination/discontinuation (maximum up to 13 days)