This is a Phase 1, open label, single dose, randomized, 2-treatment, 2-sequence, 2-period crossover study to evaluate the effect of high-fat meal on the relative bioavailability of PF-07321332 boosted with ritonavir following single dose oral administration of PF-07321332 in combination with ritonavir using 150 mg tablet formulation of PF-07321332 in healthy adult participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
Single oral dose of PF-07321332 300 mg (2 × 150 mg tablets)/ritonavir 100 mg under fed or fasted conditions at 0 hour on Day 1
Single oral dose of ritonavir 100 mg at -12 hours prior to PF-07321332/ritonavir dosing, and ritonavir 100 mg will be dosed at 12 hours after PF-07321332/ritonavir dosing.
New Haven Clinical Research Unit
New Haven, Connecticut, United States
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07321332
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration was determined by linear/log trapezoidal method and reported in this outcome measure.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose on Day 1 of Period 1 and 2
Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07321332
AUCinf was calculated by AUClast + (Clast/kel). AUClast was the area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (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 log-linear concentration-time curve.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose on Day 1 of Period 1 and 2
Maximum Observed Plasma Concentration (Cmax) of PF-07321332
Cmax was defined as maximum observed plasma concentration. It was observed directly from data.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose on Day 1 of Period 1 and 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332
Tmax was defined as the time to reach maximum observed plasma concentration of PF-07321332.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose on Day 1 of Period 1 and 2
Terminal Elimination Half-life (t1/2) of PF-07321332
t1/2 was calculated by Loge(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
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Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose on Day 1 of Period 1 and 2
Apparent Clearance (CL/F) of PF-07321332 From Plasma
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 clearance) is influenced by the fraction of the dose absorbed. CL/F was calculated as dose/AUCinf.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose on Day 1 of Period 1 and 2
Apparent Volume of Distribution (Vz/F) of PF-07321332
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. Vz/F was calculated as dose/(AUCinf\*kel). kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 48 hours post-dose on Day 1 of Period 1 and 2
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE which resulted in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to maximum of 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Day 1 of dosing in the study up to maximum of 35 days after last dose of study drug (approximately maximum of 40 days)
Number of Participants With Clinical Laboratory Abnormalities
Clinical laboratory abnormalities included following criteria: a) hematology evaluation included eosinophils/leukocytes greater than (\>) 1.2\* upper limit of normal (ULN), monocytes/leukocytes \>1.2\*ULN; b) clinical chemistry evaluation included urobilinogen greater than or equal to (\>=) 1, fibrinogen \>1.25\*baseline; c) urinalysis evaluation included urine hemoglobin \>=1.
Time frame: Day -1 of Period 1 up to Day 3 of Period 2 (maximum of 8 days)
Number of Participants Meeting Pre-Specified Criteria for Vital Signs
Vital signs evaluations included supine blood pressure (BP) and pulse rate. The pre specified criteria for vital signs included systolic blood pressure (BP) minimum (min.) less than (\<) 90 millimeter of mercury (mmHg); systolic BP change from baseline maximum (max.) decrease \>= 30 mmHg, max. increase \>=30 mmHg; diastolic BP min. \<50mmHg; diastolic BP change from baseline max. decrease \>=20, max. increase \>=20; supine pulse rate min. \<40 beats per minute (bpm) and max. \>120 bpm.
Time frame: Day 1 (pre-dose) of Period 1 up to Day 3 of Period 2 (maximum of 7 days)
Number of Participants Meeting Pre-Specified Criteria for 12-Lead Electrocardiogram (ECG) Values
A 12-lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QT, and QTc intervals and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. The pre specified criteria for ECG values included absolute value of QTCF (Fridericia's correction formula): \>=450 to less than or equal to (\<=) 480 milliseconds, \>480 to \<=500 milliseconds, \>500 milliseconds, increase from baseline \>30 - \<=60, increase from baseline \>60. PR interval: \>=300 milliseconds, increase from baseline: baseline \>200 milliseconds and max. increase \>=25% and baseline \<=200 milliseconds and max. increase \>=50%; QRS duration: \>=140 milliseconds, increase from baseline \>=50%.
Time frame: Day 1 (pre-dose) of Period 1 up to Day 3 of Period 2 (maximum of 7 days)