Food Effect Study to Evaluate the Effect of High-Fat Meal on the Relative Bioavailability of PF-07321332 Boosted With Ritonavir in Healthy Adult Participants

Healthy Participants Clinical Trial

Official title:

A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE DOSE, 2 SEQUENCE, 2 PERIOD CROSSOVER STUDY TO EVALUATE THE EFFECT OF HIGH-FAT MEAL ON THE RELATIVE BIOAVAILABILITY OF PF-07321332 BOOSTED WITH RITONAVIR IN HEALTHY ADULT PARTICIPANTS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05129475
• Other study ID #: C4671019
• Status: Completed
• Phase: Phase 1
• Start date: November 12, 2021
• Est. completion date: January 12, 2022

Study information

• Verified date: December 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 12, 2022
• Est. primary completion date: January 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and 12-lead ECGs. Female participants of childbearing potential must have a negative pregnancy test.

• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

• Positive test result (RT-PCR) for SARS-CoV-2 infection at the time of Screening or Day -1.

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

• Clinically relevant abnormalities requiring treatment (eg, acute myocardial infarction, unstable ischemic conditions, evidence of ventricular dysfunction, serious tachy- or brady brady-arrhythmias) or indicating serious underlying heart disease (eg, prolonged PR interval, cardiomyopathy, heart failure, underlying structural heart disease, Wolff Parkinson-White syndrome).

• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).

• History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.

• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg,. contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• PF-07321332/ritonavir
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
• Ritonavir
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.

Locations

Country	Name	City	State
United States	New Haven Clinical Research Unit	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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
Primary	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.	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
Primary	Maximum Observed Plasma Concentration (Cmax) of PF-07321332	Cmax was defined as maximum observed plasma concentration. It was observed directly from data.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	Day 1 of dosing in the study up to maximum of 35 days after last dose of study drug (approximately maximum of 40 days)
Secondary	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.	Day -1 of Period 1 up to Day 3 of Period 2 (maximum of 8 days)
Secondary	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.	Day 1 (pre-dose) of Period 1 up to Day 3 of Period 2 (maximum of 7 days)
Secondary	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%.	Day 1 (pre-dose) of Period 1 up to Day 3 of Period 2 (maximum of 7 days)

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